Influenza Infection (Homo sapiens)

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53403858, 65, 7215, 20, 29, 35, 5925, 63, 643, 26, 57, 7113, 349, 4424, 5610, 19, 37, 662768, 725312, 20, 48, 702864136, 17, 49, 5411427314, 18, 31, 51614533536464322, 43, 55, 60395322, 674, 23, 5546476, 17, 30, 507, 15, 26, 5741, 555, 3651, 52, 62135321111nucleoplasmcytosolendocytic vesicle membraneGolgi membraneendoplasmic reticulum membraneRPL3 Genomic RNA Segment6 SAPB1 Genomic RNA Segment1 NUP35 RPL24 M1 NUP98-5 NP HA folded andglycosylated Crm1:Ran GTPase:GDPPA Genomic RNA Segment1 CLTA Genomic RNA Segment8 Genomic RNA Segment1 NP NEP/NS2 Segment 8 RNPRNPComplex:KaryopherinalphaGenomic RNA Segment5 Genomic RNA Segment6 PA Genomic RNA Segment6 Genomic RNA Segment1 PA RPL23 NUP62 Genomic RNA Segment4 NUP98-5 PB2 PB1 RPL12 Genomic RNA Segment8 Mature intronlesstranscript derivedmRNAGenomic RNA Segment1 NP Genomic RNA Segment8 NP Glycosylated andfolded HA trimerPB2 PB2Nup45 RPS13 NEP/NS2 NPNEP/NS2 NEP/NS2 KPNB1 POLR2E M1 M2 Genomic RNA Segment3 Genomic RNA Segment6 RPS11 5.8S rRNA M1 Initiated vRNA-cRNAComplexSegment 7 RNPNP PA NP Nup45 NPNUP43 PB2 Genomic RNA Segment8 PB2 PA PB2 Genomic RNA Segment3 M1PB2 Genomic RNA Segment7 vRNP destined forExportGenomic RNA Segment4 PB2 Genomic RNA Segment4 NP Initiated vRNATranscriptionComplexGenomic RNA Segment8 NUP153 M2 RPS5 XPO1 Glycosylated NATetramerNEP/NS2 NUP50 Genomic RNA Segment7 PB2 PB2 POLR2I RPL10 NP PA Segment 2 RNPGenomic RNA Segment7 Genomic RNA Segment1 HA2 POLR2H PB1 Gycosylated NATetramerGenomic RNA Segment4 Genomic RNA Segment3 Glycosylated andfolded HA NEP/NS2 Genomic RNA Segment8 Genomic RNA Segment3 Genomic RNA Segment4 Genomic RNA Segment3 RBM5 SRSF7 NUP210 Genomic RNA Segment5 NP mRNA vRNP:M1:NEP:NPNA RPLP2 Genomic RNA Segment4 NUP214 NUP85 Genomic RNA Segment1 PB2 NUPL2 M2 TetramerKPNB1DNAJC3vRNA (genomic)PB2 RPS2 HA1 Genomic RNA Segment5 Gycosylated NATetramer:Lipid RaftInter-MembraneSpanning HA2 RPL11 PB1 RAE1 M2 RPS19 M1 TPR Genomic RNA Segment3 RPS26 M1 NUP155 NP Genomic RNA Segment2 NS2 mRNA M1RPL22 M2 PB1 PB1 PB2 Glycosylated andfolded HAM1 RPS24 Genomic RNA Segment2 palmitylated M2TetramerFAU PB2 Genomic RNA Segment4 Genomic RNA Segment4 PA PB1-F2Genomic RNA Segment8 NEP/NS2 RPL34 NUP205 NEP/NS2 NP RPL3L PB2 M2 TetramerPB2 NP NA PB1 Genomic RNA Segment6 M1 Genomic RNA Segment8 PA Nuclear Pore Complex(NPC)NP AAAS M1PA Genomic RNA Segment2 PB1 Genomic RNA Segment4 Sialic Acid BoundInfluenza A ViralParticleM2 NCBP2 HA folded,glycosylated, andpalmitylated RPL14 NEP/NS2 HNRNPC Genomic RNA Segment8 M2SRSF1 PAGenomic RNA Segment6 POLR2F Genomic RNA Segment2 PB2 PB1 Genomic RNA Segment1 Genomic RNA Segment3 Genomic RNA Segment7 HA2 RPS8 Genomic RNA Segment7 Genomic RNA Segment3 Genomic RNA Segment3 Spliceosomal EComplexM1 mRNAGenomic RNA Segment8 Genomic RNA Segment2 NCBP1 NS1 mRNAGlycosylated NA Genomic RNA Segment4 NA SNRPG Viral PolymerasePB1 Genomic RNA Segment7 RAN Genomic RNA Segment3 Segment 6 RNPSA Influenza A ViralParticleGenomic RNA Segment2 Genomic RNA Segment2 M2 PB2 SNRPA NP NUP188 GTF2F1 U1 snRNA RPS4Y1 PA PB1NP SAGenomic RNA Segment2 viral mRNANP RPL7A Genomic RNA Segment4 Glycosylated,palmitylated andfolded HAtrimer:Lipid RaftComplexLipid RaftGenomic RNA Segment5 RPL17 NA ALYREF SRSF9 Ribonucleoprotein(RNP) ComplexPB1 Glycosylated,palmitylated andfolded HA trimerRPS18 SMC1A Glycosylated NA Glycosylated NA RPL38 NP NP:Lipid RaftHA1 Influenza A ViralParticle Docked AtThe EndocyticVesicle MembraneWith An Open PoreM1 GTF2F2 RPS25 Genomic RNA Segment1 CANXM1 PB2 NEP/NS2 PA Genomic RNA Segment5 NP Genomic RNA Segment4 NA Genomic RNA Segment5 Nuclear Pore Complex(NPC)RPS27 Genomic RNA Segment5 palmitylated M2 HNRNPK POLR2B PiNEP/NS2 PB1 palmitylated M2 RPL10A Genomic RNA Segment3 HSP90AA1cRNPGenomic RNA Segment8 NP Genomic RNA Segment5 P1 mRNA M1 POLR2E Genomic RNA Segment1 PCBP1 Glycosylated NA PA Genomic RNA Segment1 Genomic RNA Segment2 Genomic RNA Segment3 M2 HA1 PA Genomic RNA Segment7 PB1 Glycosylated NA HNRNPM RNP pre-assemblycomplexGenomic RNA Segment2 Genomic RNA Segment5 RPL39 PB1 Genomic RNA Segment6 Genomic RNA Segment5 Genomic RNA Segment7 PA mRNA Genomic RNA Segment6 Genomic RNA Segment6 Genomic RNA Segment1 Genomic RNA Segment2 Genomic RNA Segment6 Gycosylated NATetramer:Lipid RaftGlycosylated NAGenomic RNA Segment6 PA POLR2J NP Genomic RNA Segment5 CCAR1 NUP37 RPL26L1 HA1 NP Sialic Acid BoundInfluenza A ViralParticleHSPA1AM1 Genomic RNA Segment7 Aminoacyl-tRNAH+RPL4 HA1 NP NP PB1 NP KPNB1 Glycosylated NA NP NS1 Genomic RNA Segment8 Genomic RNA Segment6 AAAS PB2 PB1PB2 NEP/NS2 NUP88 M2 TetramerGenomic RNA Segment5 Genomic RNA Segment6 Genomic RNA Segment6 Genomic RNA Segment7 KPNA1 Glycosylated andfolded HA trimerGenomic RNA Segment8 PB1 HA2 PB1 POLR2I PB2 NUP210 M2 mRNA NEP/NS2NP PA Genomic RNA Segment4 SA RBMX PB2NEP/NS2 HA mRNA Inter-MembraneSpanning HA2 FUS CALRCD2BP2 PB1 DHX9 Genomic RNA Segment1 Genomic RNA Segment7 RANBP2 NEP/NS2 SRSF2 KPNA1 PA Genomic RNA Segment3 RPL35A Genomic RNA Segment8 Ribonucleoprotein(RNP) ComplexPA Mature intronlesstranscript derivedmRNA with m7G capremovedPB1 Genomic RNA Segment7 NEP/NS2Influenza A ViralParticle Docked AtThe EndocyticVesicle MembraneHNRNPL RPL41 NEP/NS2Genomic RNA Segment6 M2 mRNApalmitylated M2 POLR2G Genomic RNA Segment8 PB1 POLR2F HA folded,glycosylated, andpalmitylated palmitylated M2 PB2 Glycosylated NA HNRNPA0 Clathrinp-S5-POLR2A Genomic RNA Segment6 RNAPolymeraseII(phosphorylated):TFIIF:capped pre-mRNAGenomic RNA Segment1 PB2 RPL36 M1 POLR2A POLR2L PA NP Genomic RNA Segment5 PB2 Viral ProteinsPOM121 M1 NUPL2 Genomic RNA Segment6 NUP62 Genomic RNA Segment4 PB2 PCBP2 Genomic RNA Segment4 RPL37 M2 Genomic RNA Segment2 Genomic RNA Segment2 NP vRNA TranscriptionComplexGenomic RNA Segment1 SNRPD2 Genomic RNA Segment7 PB2 M2 Intracellularassembly complexGenomic RNA Segment7 NUP155 Segment 3 RNPSRSF5 SNRNP70 PB2 Segment 4 RNPNUP43 NEP/NS2 HAGenomic RNA Segment2 PB2 SUGP1 5S rRNA Genomic RNA Segment3 H+ POLR2K vRNP Export ComplexPB2 RPS3 Genomic RNA Segment2 PANUP160 Genomic RNA Segment1 XPO1NP Genomic RNA Segment1 POLR2H Genomic RNA Segment5 Genomic RNA Segment4 Genomic RNA Segment3 Genomic RNA Segment3 Genomic RNA Segment7 Glycosylated,palmitylated andfolded HA trimerGenomic RNA Segment1 Genomic RNA Segment2 POLR2L Genomic RNA Segment5 Genomic RNA Segment8 RPL6 NEP/NS2 NUP133 M1 Genomic RNA Segment8 KPNA1Genomic RNA Segment5 Genomic RNA Segment8 HNRNPH2 PA GTF2F2 RPS27A(77-156) 2xMe-SNRPB Initiated cRNA-vRNAComplexGenomic RNA Segment6 RPL13A Genomic RNA Segment4 HNRNPF NP:Lipid RaftNUP37 Genomic RNA Segment3 Genomic RNA Segment8 Glycosylated NATetramerGenomic RNA Segment6 NS1 mRNA NEP/NS2 RPSA Genomic RNA Segment2 Genomic RNA Segment7 HA folded,glycosylated, andpalmitylated RPS15 Genomic RNA Segment7 NAM1 Genomic RNA Segment8 HA folded,glycosylated, andpalmitylated PB1 RPS9 NAGenomic RNA Segment7 PB1 vRNA (Genomic):NPComplexKPNA1 RPL15 palmitylated M2 NUP160 M2 KPNB1Influenza A ViralEnvelope InsertedInto The EndocyticVesicle MembraneNUP107 SEH1L-2 HNRNPA1 PB1 NEP/NS2 Genomic RNA Segment7 Genomic RNA Segment4 NP POLR2C Genomic RNA Segment3 NP Genomic RNA Segment2 TPR Genomic RNA Segment2 Genomic RNA Segment2 NUP107 Influenza A ViralParticleRANBP2 NP Genomic RNA Segment6 PB1 POM121 RPL5 RPL26 Genomic RNA Segment8 NUP54 PB1 mRNAGenomic RNA Segment7 RPS17 KPNA1Genomic RNA Segment7 Genomic RNA Segment1 7-methylguanosinecap RPS29 POLR2G Genomic RNA Segment5 PB2 RNP:Karyopherinalpha:Karyopherinbeta complexPB2 Genomic RNA Segment5 NP Genomic RNA Segment2 Genomic RNA Segment1 RPS4X NUP85 PB1 Genomic RNA Segment3 HNRNPUL1 RPL36A HA1 NS2 mRNARPS15A Genomic RNA Segment6 IPO52xMe-SNRPD3 Glycosylated NA Genomic RNA Segment4 RNP:Karyopherinalpha:Karyopherinbeta complexRPS23 Genomic RNA Segment5 SEH1L-2 Genomic RNA Segment6 RAE1 PB1 Acidified InfluenzaA Viral ParticleDocked At TheEndocytic VesicleMembrane With AnOpen PoreM1 GRSF1Genomic RNA Segment8 RAN RPS21 Genomic RNA Segment8 Genomic RNA Segment6 SRSF3 Genomic RNA Segment4 NEP/NS2 Genomic RNA Segment3 viral mRNASNRPE Genomic RNA Segment5 Genomic RNA Segment7 Genomic RNA Segment5 PA Genomic RNA Segment1 Genomic RNA Segment6 Elongated vRNA-mRNAComplexM1 Segment 5 RNPYBX1 NEP/NS2 Genomic RNA Segment3 NTPRPS16 NS1POLR2J RPL40 palmitylated M2 PTBP1 SNRPF NP Genomic RNA Segment2 PA U2AF1 NP RPL18A NP PA Genomic RNA Segment3 PB2 POLR2C NUP93 HNRNPA2B1 HA1 RPL30 Genomic RNA Segment3 NUP50 Genomic RNA Segment8 RPL37A POLR2D RPLP0 PA Genomic RNA Segment2 Genomic RNA Segment3 RPL32 2xMe-SNRPD1 HNRNPR PB1 PB1 Genomic RNA Segment5 NUP93 PB1 Genomic RNA Segment6 Genomic RNA Segment7 PB2 NUP153 GTF2F1 GDP M1NUP133 Glycosylated,palmitylated andfolded HAtrimer:Lipid RaftComplexNFX.1 Segment 1 RNPPA RPL18 Genomic RNA Segment7 Genomic RNA Segment5 M1 NUPL1-2 PA Ran GTPase:GTPPB1 RPL29 Genomic RNA Segment3 PB2 XPO1 NEP/NS2 NUP214 18S rRNA SRSF6 PB1 RPL7 Genomic RNA Segment6 PB2 vRNPRPS20 RPS10 M1 Genomic RNA Segment2 NS2 mRNApalmitylated M2TetramerGlycosylated NATetramerRPL27 palmitylated M2 NUP205 Genomic RNA Segment3 Genomic RNA Segment5 PA Genomic RNA Segment5 HA1 Genomic RNA Segment8 RPS14 PA Genomic RNA Segment2 RPL21 HA2 RNPS1 PA HNRNPH1 Glycosylated NA Host Derived LipidBilayer MembraneRich InSphingolipids AndCholesterolHA folded,glycosylated, andpalmitylated Genomic RNA Segment7 NP RPS7 POLR2B HA1 NUP188 Genomic RNA Segment1 RPL13 Genomic RNA Segment8 POLR2D 80S ribosomeGenomic RNA Segment8 RPLP1 PA NUP35 Genomic RNA Segment1 SRRM1 RPL9 HA folded andglycosylated Genomic RNA Segment4 Genomic RNA Segment6 RPL28 Viral ProteinsGenomic RNA Segment4 M1 vRNP:M1:NEPGenomic RNA Segment4 NA PB1 Genomic RNA Segment1 Inter-MembraneSpanning HA2 NP NUP88 U2AF2 28S rRNA Genomic RNA Segment7 GTP HNRNPD NA mRNA Genomic RNA Segment3 PB2 H+RPL8 RPL19 PA M2 mRNAGenomic RNA Segment1 PB1 NUPL1-2 RPS28 M1 PA NP PA NEP/NS2 Genomic RNA Segment4 PA POLR2K NUP54 Genomic RNA Segment7 NP PB1 Glycosylated andfolded HA trimerInfluenza cRNA(complete)HA1 HA2 Genomic RNA Segment4 Genomic RNA Segment2 RPL35 PB1 vRNP:M1 for ExportGenomic RNA Segment5 RPS12 M1 Genomic RNA Segment4 M1 Genomic RNA Segment5 RPS3A RPL27A NEP/NS2 PA NPInfluenza A ViralParticle With AFusion CompetentHA2NP Genomic RNA Segment1 Cleaved HA InfluenzaA Viral ParticleM1 mRNA Genomic RNA Segment4 HNRNPU RPS6 RPL23A Glycosylated NA Inter-MembraneSpanning HA2 Glycosylated NA Genomic RNA Segment1 PB1 Genomic RNA Segment8 Genomic RNA Segment2 RPL31 M1 PA HA folded,glycosylated, andpalmitylated Glycosylated NA PA Genomic RNA Segment4 HNRNPA3 8, 16, 698, 16, 69


Description

The virus particle initially associates with a human host cell by binding to sialic acid-containing receptors on the host cell surface. The bound virus is endocytosed by one of four distinct mechanisms. The low endosomal pH sets in motion a number of steps that lead to viral membrane fusion mediated by the viral hemagglutinin (HA) protein, and the eventual release of the uncoated viral ribonucleoprotein complex into the cytosol of the host cell. The ribonucleoprotein complex is transported through the nuclear pore into the nucleus. Once in the nucleus, the incoming negative-sense viral RNA (vRNA) is transcribed into messenger RNA (mRNA) by a primer-dependent mechanism. Replication occurs via a two step process. A full-length complementary RNA (cRNA), a positive-sense copy of the vRNA, is first made and this in turn is used as a template to produce more vRNA. The viral proteins are expressed and processed and eventually assemble with vRNAs at budding sites within the host cell membrane. The viral protein complexes and ribonucleoproteins are assembled into viral particles and bud from the host cell, enveloped in the host cell's membrane.

This release contains a framework for the further annotation of the viral life-cycle. Source:Reactome.</div>

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  1. Honda A, Mizumoto K, Ishihama A.; ''Two separate sequences of PB2 subunit constitute the RNA cap-binding site of influenza virus RNA polymerase.''; PubMed Europe PMC Scholia
  2. Cros JF, García-Sastre A, Palese P.; ''An unconventional NLS is critical for the nuclear import of the influenza A virus nucleoprotein and ribonucleoprotein.''; PubMed Europe PMC Scholia
  3. Lamb RA, Choppin PW, Chanock RM, Lai CJ.; ''Mapping of the two overlapping genes for polypeptides NS1 and NS2 on RNA segment 8 of influenza virus genome.''; PubMed Europe PMC Scholia
  4. Li Y, Chen ZY, Wang W, Baker CC, Krug RM.; ''The 3'-end-processing factor CPSF is required for the splicing of single-intron pre-mRNAs in vivo.''; PubMed Europe PMC Scholia
  5. Lin DH, Stuwe T, Schilbach S, Rundlet EJ, Perriches T, Mobbs G, Fan Y, Thierbach K, Huber FM, Collins LN, Davenport AM, Jeon YE, Hoelz A.; ''Architecture of the symmetric core of the nuclear pore.''; PubMed Europe PMC Scholia
  6. Plotch SJ, Krug RM.; ''Influenza virion transcriptase: synthesis in vitro of large, polyadenylic acid-containing complementary RNA.''; PubMed Europe PMC Scholia
  7. Robertson JS, Schubert M, Lazzarini RA.; ''Polyadenylation sites for influenza virus mRNA.''; PubMed Europe PMC Scholia
  8. Liu C, Eichelberger MC, Compans RW, Air GM.; ''Influenza type A virus neuraminidase does not play a role in viral entry, replication, assembly, or budding.''; PubMed Europe PMC Scholia
  9. Wang C, Takeuchi K, Pinto LH, Lamb RA.; ''Ion channel activity of influenza A virus M2 protein: characterization of the amantadine block.''; PubMed Europe PMC Scholia
  10. Rabut G, Doye V, Ellenberg J.; ''Mapping the dynamic organization of the nuclear pore complex inside single living cells.''; PubMed Europe PMC Scholia
  11. Neumann G, Castrucci MR, Kawaoka Y.; ''Nuclear import and export of influenza virus nucleoprotein.''; PubMed Europe PMC Scholia
  12. Heino S, Lusa S, Somerharju P, Ehnholm C, Olkkonen VM, Ikonen E.; ''Dissecting the role of the golgi complex and lipid rafts in biosynthetic transport of cholesterol to the cell surface.''; PubMed Europe PMC Scholia
  13. Scheiffele P, Roth MG, Simons K.; ''Interaction of influenza virus haemagglutinin with sphingolipid-cholesterol membrane domains via its transmembrane domain.''; PubMed Europe PMC Scholia
  14. Fontoura BM, Blobel G, Matunis MJ.; ''A conserved biogenesis pathway for nucleoporins: proteolytic processing of a 186-kilodalton precursor generates Nup98 and the novel nucleoporin, Nup96.''; PubMed Europe PMC Scholia
  15. Ori A, Banterle N, Iskar M, Iskar M, Andrés-Pons A, Escher C, Khanh Bui H, Sparks L, Solis-Mezarino V, Rinner O, Bork P, Lemke EA, Beck M.; ''Cell type-specific nuclear pores: a case in point for context-dependent stoichiometry of molecular machines.''; PubMed Europe PMC Scholia
  16. Kabachinski G, Schwartz TU.; ''The nuclear pore complex--structure and function at a glance.''; PubMed Europe PMC Scholia
  17. Ma K, Roy AM, Whittaker GR.; ''Nuclear export of influenza virus ribonucleoproteins: identification of an export intermediate at the nuclear periphery.''; PubMed Europe PMC Scholia
  18. Poon LL, Pritlove DC, Sharps J, Brownlee GG.; ''The RNA polymerase of influenza virus, bound to the 5' end of virion RNA, acts in cis to polyadenylate mRNA.''; PubMed Europe PMC Scholia
  19. Engelhardt OG, Fodor E.; ''Functional association between viral and cellular transcription during influenza virus infection.''; PubMed Europe PMC Scholia
  20. Jones IM, Reay PA, Philpott KL.; ''Nuclear location of all three influenza polymerase proteins and a nuclear signal in polymerase PB2.''; PubMed Europe PMC Scholia
  21. Area E, Martín-Benito J, Gastaminza P, Torreira E, Valpuesta JM, Carrascosa JL, Ortín J.; ''3D structure of the influenza virus polymerase complex: localization of subunit domains.''; PubMed Europe PMC Scholia
  22. Noah DL, Twu KY, Krug RM.; ''Cellular antiviral responses against influenza A virus are countered at the posttranscriptional level by the viral NS1A protein via its binding to a cellular protein required for the 3' end processing of cellular pre-mRNAS.''; PubMed Europe PMC Scholia
  23. Westera L, Jennings AM, Maamary J, Schwemmle M, García-Sastre A, Bortz E.; ''Poly-ADP Ribosyl Polymerase 1 (PARP1) Regulates Influenza A Virus Polymerase.''; PubMed Europe PMC Scholia
  24. Doms RW, Lamb RA, Rose JK, Helenius A.; ''Folding and assembly of viral membrane proteins.''; PubMed Europe PMC Scholia
  25. Chen Z, Li Y, Krug RM.; ''Influenza A virus NS1 protein targets poly(A)-binding protein II of the cellular 3'-end processing machinery.''; PubMed Europe PMC Scholia
  26. Molinari M, Helenius A.; ''Chaperone selection during glycoprotein translocation into the endoplasmic reticulum.''; PubMed Europe PMC Scholia
  27. Cronshaw JM, Krutchinsky AN, Zhang W, Chait BT, Matunis MJ.; ''Proteomic analysis of the mammalian nuclear pore complex.''; PubMed Europe PMC Scholia
  28. Alonso-Caplen FV, Nemeroff ME, Qiu Y, Krug RM.; ''Nucleocytoplasmic transport: the influenza virus NS1 protein regulates the transport of spliced NS2 mRNA and its precursor NS1 mRNA.''; PubMed Europe PMC Scholia
  29. McCown MF, Pekosz A.; ''The influenza A virus M2 cytoplasmic tail is required for infectious virus production and efficient genome packaging.''; PubMed Europe PMC Scholia
  30. Luo GX, Luytjes W, Enami M, Palese P.; ''The polyadenylation signal of influenza virus RNA involves a stretch of uridines followed by the RNA duplex of the panhandle structure.''; PubMed Europe PMC Scholia
  31. Saito T, Taylor G, Webster RG.; ''Steps in maturation of influenza A virus neuraminidase.''; PubMed Europe PMC Scholia
  32. Hagen M, Chung TD, Butcher JA, Krystal M.; ''Recombinant influenza virus polymerase: requirement of both 5' and 3' viral ends for endonuclease activity.''; PubMed Europe PMC Scholia
  33. Hausmann J, Kretzschmar E, Garten W, Klenk HD.; ''Biosynthesis, intracellular transport and enzymatic activity of an avian influenza A virus neuraminidase: role of unpaired cysteines and individual oligosaccharides.''; PubMed Europe PMC Scholia
  34. Wang P, Palese P, O'Neill RE.; ''The NPI-1/NPI-3 (karyopherin alpha) binding site on the influenza a virus nucleoprotein NP is a nonconventional nuclear localization signal.''; PubMed Europe PMC Scholia
  35. Ye Q, Krug RM, Tao YJ.; ''The mechanism by which influenza A virus nucleoprotein forms oligomers and binds RNA.''; PubMed Europe PMC Scholia
  36. Stegmann T.; ''Membrane fusion mechanisms: the influenza hemagglutinin paradigm and its implications for intracellular fusion.''; PubMed Europe PMC Scholia
  37. Shimizu K, Iguchi A, Gomyou R, Ono Y.; ''Influenza virus inhibits cleavage of the HSP70 pre-mRNAs at the polyadenylation site.''; PubMed Europe PMC Scholia
  38. Park CJ, Bae SH, Lee MK, Varani G, Choi BS.; ''Solution structure of the influenza A virus cRNA promoter: implications for differential recognition of viral promoter structures by RNA-dependent RNA polymerase.''; PubMed Europe PMC Scholia
  39. Neumann G, Hughes MT, Kawaoka Y.; ''Influenza A virus NS2 protein mediates vRNP nuclear export through NES-independent interaction with hCRM1.''; PubMed Europe PMC Scholia
  40. Barman S, Ali A, Hui EK, Adhikary L, Nayak DP.; ''Transport of viral proteins to the apical membranes and interaction of matrix protein with glycoproteins in the assembly of influenza viruses.''; PubMed Europe PMC Scholia
  41. Elster C, Fourest E, Baudin F, Larsen K, Cusack S, Ruigrok RW.; ''A small percentage of influenza virus M1 protein contains zinc but zinc does not influence in vitro M1-RNA interaction.''; PubMed Europe PMC Scholia
  42. O'Neill RE, Jaskunas R, Blobel G, Palese P, Moroianu J.; ''Nuclear import of influenza virus RNA can be mediated by viral nucleoprotein and transport factors required for protein import.''; PubMed Europe PMC Scholia
  43. Daniels R, Kurowski B, Johnson AE, Hebert DN.; ''N-linked glycans direct the cotranslational folding pathway of influenza hemagglutinin.''; PubMed Europe PMC Scholia
  44. Askjaer P, Jensen TH, Nilsson J, Englmeier L, Kjems J.; ''The specificity of the CRM1-Rev nuclear export signal interaction is mediated by RanGTP.''; PubMed Europe PMC Scholia
  45. Nayak DP, Hui EK, Barman S.; ''Assembly and budding of influenza virus.''; PubMed Europe PMC Scholia
  46. Cianci C, Tiley L, Krystal M.; ''Differential activation of the influenza virus polymerase via template RNA binding.''; PubMed Europe PMC Scholia
  47. Nemergut ME, Lindsay ME, Brownawell AM, Macara IG.; ''Ran-binding protein 3 links Crm1 to the Ran guanine nucleotide exchange factor.''; PubMed Europe PMC Scholia
  48. Detjen BM, St Angelo C, Katze MG, Krug RM.; ''The three influenza virus polymerase (P) proteins not associated with viral nucleocapsids in the infected cell are in the form of a complex.''; PubMed Europe PMC Scholia
  49. Li ML, Ramirez BC, Krug RM.; ''RNA-dependent activation of primer RNA production by influenza virus polymerase: different regions of the same protein subunit constitute the two required RNA-binding sites.''; PubMed Europe PMC Scholia
  50. Kash JC, Goodman AG, Korth MJ, Katze MG.; ''Hijacking of the host-cell response and translational control during influenza virus infection.''; PubMed Europe PMC Scholia
  51. Pleschka S, Wolff T, Ehrhardt C, Hobom G, Planz O, Rapp UR, Ludwig S.; ''Influenza virus propagation is impaired by inhibition of the Raf/MEK/ERK signalling cascade.''; PubMed Europe PMC Scholia
  52. Mukaigawa J, Nayak DP.; ''Two signals mediate nuclear localization of influenza virus (A/WSN/33) polymerase basic protein 2.''; PubMed Europe PMC Scholia
  53. Honda A, Uéda K, Nagata K, Ishihama A.; ''RNA polymerase of influenza virus: role of NP in RNA chain elongation.''; PubMed Europe PMC Scholia
  54. Brownlee GG, Sharps JL.; ''The RNA polymerase of influenza a virus is stabilized by interaction with its viral RNA promoter.''; PubMed Europe PMC Scholia
  55. Crow M, Deng T, Addley M, Brownlee GG.; ''Mutational analysis of the influenza virus cRNA promoter and identification of nucleotides critical for replication.''; PubMed Europe PMC Scholia
  56. Vreede FT, Jung TE, Brownlee GG.; ''Model suggesting that replication of influenza virus is regulated by stabilization of replicative intermediates.''; PubMed Europe PMC Scholia
  57. Krug RM.; ''Priming of influenza viral RNA transcription by capped heterologous RNAs.''; PubMed Europe PMC Scholia
  58. Bergmann M, Garcia-Sastre A, Carnero E, Pehamberger H, Wolff K, Palese P, Muster T.; ''Influenza virus NS1 protein counteracts PKR-mediated inhibition of replication.''; PubMed Europe PMC Scholia
  59. Yasuda J, Nakada S, Kato A, Toyoda T, Ishihama A.; ''Molecular assembly of influenza virus: association of the NS2 protein with virion matrix.''; PubMed Europe PMC Scholia
  60. Sugrue RJ, Belshe RB, Hay AJ.; ''Palmitoylation of the influenza A virus M2 protein.''; PubMed Europe PMC Scholia
  61. Chen W, Calvo PA, Malide D, Gibbs J, Schubert U, Bacik I, Basta S, O'Neill R, Schickli J, Palese P, Henklein P, Bennink JR, Yewdell JW.; ''A novel influenza A virus mitochondrial protein that induces cell death.''; PubMed Europe PMC Scholia
  62. Luo C, Nobusawa E, Nakajima K.; ''An analysis of the role of neuraminidase in the receptor-binding activity of influenza B virus: the inhibitory effect of Zanamivir on haemadsorption.''; PubMed Europe PMC Scholia
  63. Marjuki H, Alam MI, Ehrhardt C, Wagner R, Planz O, Klenk HD, Ludwig S, Pleschka S.; ''Membrane accumulation of influenza A virus hemagglutinin triggers nuclear export of the viral genome via protein kinase Calpha-mediated activation of ERK signaling.''; PubMed Europe PMC Scholia
  64. Suntharalingam M, Wente SR.; ''Peering through the pore: nuclear pore complex structure, assembly, and function.''; PubMed Europe PMC Scholia
  65. Li ML, Rao P, Krug RM.; ''The active sites of the influenza cap-dependent endonuclease are on different polymerase subunits.''; PubMed Europe PMC Scholia
  66. Melén K, Kinnunen L, Fagerlund R, Ikonen N, Twu KY, Krug RM, Julkunen I.; ''Nuclear and nucleolar targeting of influenza A virus NS1 protein: striking differences between different virus subtypes.''; PubMed Europe PMC Scholia
  67. Palese P, Compans RW.; ''Inhibition of influenza virus replication in tissue culture by 2-deoxy-2,3-dehydro-N-trifluoroacetylneuraminic acid (FANA): mechanism of action.''; PubMed Europe PMC Scholia
  68. Nilsson J, Askjaer P, Kjems J.; ''A role for the basic patch and the C terminus of RanGTP in regulating the dynamic interactions with importin beta, CRM1 and RanBP1.''; PubMed Europe PMC Scholia
  69. Li N, Ren A, Wang X, Fan X, Zhao Y, Gao GF, Cleary P, Wang B.; ''Influenza viral neuraminidase primes bacterial coinfection through TGF-β-mediated expression of host cell receptors.''; PubMed Europe PMC Scholia
  70. Kosinski J, Mosalaganti S, von Appen A, Teimer R, DiGuilio AL, Wan W, Bui KH, Hagen WJ, Briggs JA, Glavy JS, Hurt E, Beck M.; ''Molecular architecture of the inner ring scaffold of the human nuclear pore complex.''; PubMed Europe PMC Scholia
  71. DONALD HB, ISAACS A.; ''Counts of influenza virus particles.''; PubMed Europe PMC Scholia
  72. Chanturiya AN, Basañez G, Schubert U, Henklein P, Yewdell JW, Zimmerberg J.; ''PB1-F2, an influenza A virus-encoded proapoptotic mitochondrial protein, creates variably sized pores in planar lipid membranes.''; PubMed Europe PMC Scholia
  73. Stegmann T, Morselt HW, Scholma J, Wilschut J.; ''Fusion of influenza virus in an intracellular acidic compartment measured by fluorescence dequenching.''; PubMed Europe PMC Scholia
  74. Veit M, Klenk HD, Kendal A, Rott R.; ''The M2 protein of influenza A virus is acylated.''; PubMed Europe PMC Scholia
  75. Enami M, Sharma G, Benham C, Palese P.; ''An influenza virus containing nine different RNA segments.''; PubMed Europe PMC Scholia
  76. Braam J, Ulmanen I, Krug RM.; ''Molecular model of a eucaryotic transcription complex: functions and movements of influenza P proteins during capped RNA-primed transcription.''; PubMed Europe PMC Scholia
  77. Neumann G, Brownlee GG, Fodor E, Kawaoka Y.; ''Orthomyxovirus replication, transcription, and polyadenylation.''; PubMed Europe PMC Scholia
  78. Garman E, Laver G.; ''Controlling influenza by inhibiting the virus's neuraminidase.''; PubMed Europe PMC Scholia
  79. Ward AC, Castelli LA, Lucantoni AC, White JF, Azad AA, Macreadie IG.; ''Expression and analysis of the NS2 protein of influenza A virus.''; PubMed Europe PMC Scholia
  80. Martin K, Helenius A.; ''Transport of incoming influenza virus nucleocapsids into the nucleus.''; PubMed Europe PMC Scholia
  81. Perez DR, Donis RO.; ''Functional analysis of PA binding by influenza a virus PB1: effects on polymerase activity and viral infectivity.''; PubMed Europe PMC Scholia
  82. Nemeroff ME, Barabino SM, Li Y, Keller W, Krug RM.; ''Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs.''; PubMed Europe PMC Scholia
  83. Watanabe K, Takizawa N, Katoh M, Hoshida K, Kobayashi N, Nagata K.; ''Inhibition of nuclear export of ribonucleoprotein complexes of influenza virus by leptomycin B.''; PubMed Europe PMC Scholia
  84. Vreede FT, Brownlee GG.; ''Influenza virion-derived viral ribonucleoproteins synthesize both mRNA and cRNA in vitro.''; PubMed Europe PMC Scholia
  85. Plotch SJ, Bouloy M, Ulmanen I, Krug RM.; ''A unique cap(m7GpppXm)-dependent influenza virion endonuclease cleaves capped RNAs to generate the primers that initiate viral RNA transcription.''; PubMed Europe PMC Scholia
  86. Amorim MJ, Read EK, Dalton RM, Medcalf L, Digard P.; ''Nuclear export of influenza A virus mRNAs requires ongoing RNA polymerase II activity.''; PubMed Europe PMC Scholia
  87. Zhang J, Lamb RA.; ''Characterization of the membrane association of the influenza virus matrix protein in living cells.''; PubMed Europe PMC Scholia
  88. González S, Zürcher T, Ortín J.; ''Identification of two separate domains in the influenza virus PB1 protein involved in the interaction with the PB2 and PA subunits: a model for the viral RNA polymerase structure.''; PubMed Europe PMC Scholia
  89. Petosa C, Schoehn G, Askjaer P, Bauer U, Moulin M, Steuerwald U, Soler-López M, Baudin F, Mattaj IW, Müller CW.; ''Architecture of CRM1/Exportin1 suggests how cooperativity is achieved during formation of a nuclear export complex.''; PubMed Europe PMC Scholia
  90. Carrasco M, Amorim MJ, Digard P.; ''Lipid raft-dependent targeting of the influenza A virus nucleoprotein to the apical plasma membrane.''; PubMed Europe PMC Scholia
  91. Mikulásová A, Varecková E, Fodor E.; ''Transcription and replication of the influenza a virus genome.''; PubMed Europe PMC Scholia
  92. Nakagawa Y, Oda K, Nakada S.; ''The PB1 subunit alone can catalyze cRNA synthesis, and the PA subunit in addition to the PB1 subunit is required for viral RNA synthesis in replication of the influenza virus genome.''; PubMed Europe PMC Scholia
  93. Veit M, Kretzschmar E, Kuroda K, Garten W, Schmidt MF, Klenk HD, Rott R.; ''Site-specific mutagenesis identifies three cysteine residues in the cytoplasmic tail as acylation sites of influenza virus hemagglutinin.''; PubMed Europe PMC Scholia
  94. Palese P, Tobita K, Ueda M, Compans RW.; ''Characterization of temperature sensitive influenza virus mutants defective in neuraminidase.''; PubMed Europe PMC Scholia
  95. Pritlove DC, Fodor E, Seong BL, Brownlee GG.; ''In vitro transcription and polymerase binding studies of the termini of influenza A virus cRNA: evidence for a cRNA panhandle.''; PubMed Europe PMC Scholia
  96. Schmitt AP, Lamb RA.; ''Escaping from the cell: assembly and budding of negative-strand RNA viruses.''; PubMed Europe PMC Scholia
  97. Salom D, Hill BR, Lear JD, DeGrado WF.; ''pH-dependent tetramerization and amantadine binding of the transmembrane helix of M2 from the influenza A virus.''; PubMed Europe PMC Scholia
  98. Deng T, Vreede FT, Brownlee GG.; ''Different de novo initiation strategies are used by influenza virus RNA polymerase on its cRNA and viral RNA promoters during viral RNA replication.''; PubMed Europe PMC Scholia
  99. Boulo S, Akarsu H, Ruigrok RW, Baudin F.; ''Nuclear traffic of influenza virus proteins and ribonucleoprotein complexes.''; PubMed Europe PMC Scholia
  100. De Marcos Lousa C, Trézéguet V, Dianoux AC, Brandolin G, Lauquin GJ.; ''The human mitochondrial ADP/ATP carriers: kinetic properties and biogenesis of wild-type and mutant proteins in the yeast S. cerevisiae.''; PubMed Europe PMC Scholia
  101. Lamb RA, Lai CJ, Choppin PW.; ''Sequences of mRNAs derived from genome RNA segment 7 of influenza virus: colinear and interrupted mRNAs code for overlapping proteins.''; PubMed Europe PMC Scholia
  102. Tatu U, Hammond C, Helenius A.; ''Folding and oligomerization of influenza hemagglutinin in the ER and the intermediate compartment.''; PubMed Europe PMC Scholia
  103. Zheng H, Lee HA, Palese P, García-Sastre A.; ''Influenza A virus RNA polymerase has the ability to stutter at the polyadenylation site of a viral RNA template during RNA replication.''; PubMed Europe PMC Scholia
  104. Baudin F, Petit I, Weissenhorn W, Ruigrok RW.; ''In vitro dissection of the membrane and RNP binding activities of influenza virus M1 protein.''; PubMed Europe PMC Scholia
  105. Fortes P, Beloso A, Ortín J.; ''Influenza virus NS1 protein inhibits pre-mRNA splicing and blocks mRNA nucleocytoplasmic transport.''; PubMed Europe PMC Scholia
  106. Chen Z, Krug RM.; ''Selective nuclear export of viral mRNAs in influenza-virus-infected cells.''; PubMed Europe PMC Scholia
  107. Donelan NR, Basler CF, García-Sastre A.; ''A recombinant influenza A virus expressing an RNA-binding-defective NS1 protein induces high levels of beta interferon and is attenuated in mice.''; PubMed Europe PMC Scholia
  108. Mayer D, Molawi K, Martínez-Sobrido L, Ghanem A, Thomas S, Baginsky S, Grossmann J, García-Sastre A, Schwemmle M.; ''Identification of cellular interaction partners of the influenza virus ribonucleoprotein complex and polymerase complex using proteomic-based approaches.''; PubMed Europe PMC Scholia
  109. Fodor E, Pritlove DC, Brownlee GG.; ''The influenza virus panhandle is involved in the initiation of transcription.''; PubMed Europe PMC Scholia
  110. Bortz E, Westera L, Maamary J, Steel J, Albrecht RA, Manicassamy B, Chase G, Martínez-Sobrido L, Schwemmle M, García-Sastre A.; ''Host- and strain-specific regulation of influenza virus polymerase activity by interacting cellular proteins.''; PubMed Europe PMC Scholia
  111. Morris SJ, Price GE, Barnett JM, Hiscox SA, Smith H, Sweet C.; ''Role of neuraminidase in influenza virus-induced apoptosis.''; PubMed Europe PMC Scholia
  112. Takeda M, Leser GP, Russell CJ, Lamb RA.; ''Influenza virus hemagglutinin concentrates in lipid raft microdomains for efficient viral fusion.''; PubMed Europe PMC Scholia
  113. Veit M, Schmidt MF.; ''Timing of palmitoylation of influenza virus hemagglutinin.''; PubMed Europe PMC Scholia
  114. Son KN, Liang Z, Lipton HL.; ''Double-Stranded RNA Is Detected by Immunofluorescence Analysis in RNA and DNA Virus Infections, Including Those by Negative-Stranded RNA Viruses.''; PubMed Europe PMC Scholia
  115. Gething MJ, McCammon K, Sambrook J.; ''Expression of wild-type and mutant forms of influenza hemagglutinin: the role of folding in intracellular transport.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
115105view18:57, 25 January 2021EgonwRemoved an empty reference.
114625view16:08, 25 January 2021ReactomeTeamReactome version 75
113585view08:08, 3 November 2020EgonwRemoved the empty reference (we now know this is a book that the convertor cannot handle).
113073view11:13, 2 November 2020ReactomeTeamReactome version 74
112844view05:16, 12 October 2020EgonwRemoved an empty (and unused) reference
112308view15:22, 9 October 2020ReactomeTeamReactome version 73
101951view12:13, 20 November 2018EgonwRemoved an empty reference.
101207view11:10, 1 November 2018ReactomeTeamreactome version 66
100745view20:35, 31 October 2018ReactomeTeamreactome version 65
100289view19:12, 31 October 2018ReactomeTeamreactome version 64
99835view15:56, 31 October 2018ReactomeTeamreactome version 63
99392view14:33, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99088view12:39, 31 October 2018ReactomeTeamreactome version 62
94058view13:54, 16 August 2017ReactomeTeamreactome version 61
93687view11:31, 9 August 2017ReactomeTeamreactome version 61
87172view19:26, 18 July 2016MkutmonOntology Term : 'infectious disease pathway' added !
86810view09:27, 11 July 2016ReactomeTeamreactome version 56
83087view09:57, 18 November 2015ReactomeTeamVersion54
81411view12:56, 21 August 2015ReactomeTeamVersion53
76880view08:15, 17 July 2014ReactomeTeamFixed remaining interactions
76585view11:56, 16 July 2014ReactomeTeamFixed remaining interactions
75918view09:57, 11 June 2014ReactomeTeamRe-fixing comment source
75618view10:48, 10 June 2014ReactomeTeamReactome 48 Update
74973view13:49, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74617view08:40, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
18S rRNA ProteinX03205 (EMBL)
28S rRNA ProteinM11167 (EMBL)
2xMe-SNRPB ProteinP14678 (Uniprot-TrEMBL)
2xMe-SNRPD1 ProteinP62314 (Uniprot-TrEMBL)
2xMe-SNRPD3 ProteinP62318 (Uniprot-TrEMBL)
5.8S rRNA ProteinJ01866 (EMBL)
5S rRNA ProteinV00589 (EMBL)
7-methylguanosine cap MetaboliteCHEBI:17825 (ChEBI)
80S ribosomeComplexR-HSA-72500 (Reactome)
AAAS ProteinQ9NRG9 (Uniprot-TrEMBL)
ALYREF ProteinQ86V81 (Uniprot-TrEMBL)
Acidified Influenza

A Viral Particle Docked At The Endocytic Vesicle Membrane With An

Open Pore		ComplexR-FLU-189177 (Reactome)
Aminoacyl-tRNAR-HSA-37001 (Reactome)
CALRProteinP27797 (Uniprot-TrEMBL)
CANXProteinP27824 (Uniprot-TrEMBL)
CCAR1 ProteinQ8IX12 (Uniprot-TrEMBL)
CD2BP2 ProteinO95400 (Uniprot-TrEMBL)
CLTA ProteinP09496 (Uniprot-TrEMBL)
ClathrinComplexR-HSA-177482 (Reactome)
Cleaved HA Influenza A Viral ParticleComplexR-FLU-169239 (Reactome)
Crm1:Ran GTPase:GDPComplexR-HSA-165538 (Reactome)
DHX9 ProteinQ08211 (Uniprot-TrEMBL)
DNAJC3ProteinQ13217 (Uniprot-TrEMBL)
Elongated vRNA-mRNA ComplexComplexR-FLU-192700 (Reactome) Capped, synthesized RNA strand complementary to vRNA, plus viral polymerase and template vRNA (Plotch, 1977).
FAU ProteinP62861 (Uniprot-TrEMBL)
FUS ProteinP35637 (Uniprot-TrEMBL)
GDP MetaboliteCHEBI:17552 (ChEBI)
GRSF1ProteinQ12849 (Uniprot-TrEMBL)
GTF2F1 ProteinP35269 (Uniprot-TrEMBL)
GTF2F2 ProteinP13984 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
Genomic RNA Segment 1 ProteinAF389115 (EMBL)
Genomic RNA Segment 2 ProteinAF389116 (EMBL)
Genomic RNA Segment 3 ProteinAF389117 (EMBL)
Genomic RNA Segment 4 ProteinAF389118 (EMBL)
Genomic RNA Segment 5 ProteinAF389119 (EMBL)
Genomic RNA Segment 6 ProteinAF389120 (EMBL)
Genomic RNA Segment 7 ProteinAF389121 (EMBL)
Genomic RNA Segment 8 ProteinAF389122 (EMBL)
Glycosylated NA TetramerComplexR-FLU-195724 (Reactome)
Glycosylated NA TetramerComplexR-FLU-195775 (Reactome)
Glycosylated NA TetramerComplexR-FLU-195796 (Reactome)
Glycosylated NA ProteinP03468 (Uniprot-TrEMBL)
Glycosylated NAProteinP03468 (Uniprot-TrEMBL)
Glycosylated and folded HA ProteinP03452 (Uniprot-TrEMBL)
Glycosylated and folded HA trimerComplexR-FLU-195787 (Reactome)
Glycosylated and folded HA trimerComplexR-FLU-195803 (Reactome)
Glycosylated and folded HA trimerComplexR-FLU-195819 (Reactome)
Glycosylated and folded HAProteinP03452 (Uniprot-TrEMBL)
Glycosylated,

palmitylated and folded HA trimer:Lipid Raft

Complex		ComplexR-FLU-195723 (Reactome)
Glycosylated,

palmitylated and folded HA trimer:Lipid Raft

Complex		ComplexR-FLU-195755 (Reactome)
Glycosylated,

palmitylated and

folded HA trimer		ComplexR-FLU-195725 (Reactome)
Glycosylated,

palmitylated and

folded HA trimer		ComplexR-FLU-195738 (Reactome)
Gycosylated NA Tetramer:Lipid RaftComplexR-FLU-195735 (Reactome)
Gycosylated NA Tetramer:Lipid RaftComplexR-FLU-195736 (Reactome)
Gycosylated NA TetramerComplexR-FLU-195728 (Reactome)
H+ MetaboliteCHEBI:15378 (ChEBI)
H+MetaboliteCHEBI:15378 (ChEBI)
HA folded and glycosylated ProteinP03452 (Uniprot-TrEMBL)
HA folded,

glycosylated, and

palmitylated 		ProteinP03452 (Uniprot-TrEMBL)
HA mRNA ProteinV01088 (EMBL)
HA1 ProteinP03452 (Uniprot-TrEMBL)
HA2 ProteinP03452 (Uniprot-TrEMBL)
HAProteinP03452 (Uniprot-TrEMBL)
HNRNPA0 ProteinQ13151 (Uniprot-TrEMBL)
HNRNPA1 ProteinP09651 (Uniprot-TrEMBL)
HNRNPA2B1 ProteinP22626 (Uniprot-TrEMBL)
HNRNPA3 ProteinP51991 (Uniprot-TrEMBL)
HNRNPC ProteinP07910 (Uniprot-TrEMBL)
HNRNPD ProteinQ14103 (Uniprot-TrEMBL)
HNRNPF ProteinP52597 (Uniprot-TrEMBL)
HNRNPH1 ProteinP31943 (Uniprot-TrEMBL)
HNRNPH2 ProteinP55795 (Uniprot-TrEMBL)
HNRNPK ProteinP61978 (Uniprot-TrEMBL)
HNRNPL ProteinP14866 (Uniprot-TrEMBL)
HNRNPM ProteinP52272 (Uniprot-TrEMBL)
HNRNPR ProteinO43390 (Uniprot-TrEMBL)
HNRNPU ProteinQ00839 (Uniprot-TrEMBL)
HNRNPUL1 ProteinQ9BUJ2 (Uniprot-TrEMBL)
HSP90AA1ProteinP07900 (Uniprot-TrEMBL)
HSPA1AProteinP08107 (Uniprot-TrEMBL)
Host Derived Lipid

Bilayer Membrane Rich In Sphingolipids And

Cholesterol		R-NUL-169703 (Reactome)
IPO5ProteinO00410 (Uniprot-TrEMBL)
Influenza A Viral

Envelope Inserted Into The Endocytic

Vesicle Membrane		ComplexR-FLU-189157 (Reactome)
Influenza A Viral

Particle Docked At The Endocytic Vesicle Membrane

With An Open Pore		ComplexR-FLU-189181 (Reactome)
Influenza A Viral

Particle Docked At The Endocytic

Vesicle Membrane		ComplexR-FLU-189138 (Reactome)
Influenza A Viral

Particle With A Fusion Competent

HA2		ComplexR-FLU-189182 (Reactome)
Influenza A Viral ParticleComplexR-FLU-189171 (Reactome)
Influenza A Viral ParticleComplexR-FLU-195941 (Reactome)
Influenza cRNA (complete)R-NUL-192638 (Reactome)
Initiated cRNA-vRNA ComplexComplexR-FLU-192650 (Reactome) cRNA bound by NP and trimeric polymerase, capable of vRNA synthesis from the cRNA template.
Initiated vRNA

Transcription

Complex		ComplexR-FLU-192756 (Reactome) Viral RNA bound by polymerase PB1-PB2-PA subunits, primed by a 5' end cap cleaved from a host mRNA, and the second ribonucleotide (a G) complementary to a the vRNA second position (a C, Beaton, 1981; Krug, 1981; Li, 2001).
Initiated vRNA-cRNA ComplexComplexR-FLU-192901 (Reactome) vRNA bound by NP and trimeric polymerase, capable of complementary RNA synthesis.
Inter-Membrane Spanning HA2 ProteinP03452 (Uniprot-TrEMBL)
Intracellular assembly complexComplexR-FLU-195925 (Reactome)
KPNA1 ProteinP52294 (Uniprot-TrEMBL)
KPNA1ProteinP52294 (Uniprot-TrEMBL)
KPNB1 ProteinQ14974 (Uniprot-TrEMBL)
KPNB1ProteinQ14974 (Uniprot-TrEMBL)
Lipid RaftR-NUL-195764 (Reactome)
M1 ProteinP03485 (Uniprot-TrEMBL)
M1 mRNA ProteinAF389121 (EMBL)
M1 mRNARnaAF389121 (EMBL)
M1ProteinP03485 (Uniprot-TrEMBL)
M2 ProteinP06821 (Uniprot-TrEMBL)
M2 TetramerComplexR-FLU-195727 (Reactome)
M2 TetramerComplexR-FLU-195794 (Reactome)
M2 TetramerComplexR-FLU-195797 (Reactome)
M2 mRNA ProteinAF389121 (EMBL)
M2 mRNARnaAF389121 (EMBL)
M2ProteinP06821 (Uniprot-TrEMBL)
Mature intronless

transcript derived mRNA with m7G cap

removed		R-NUL-193039 (Reactome) A mature mRNA that has been 3' cleaved, subsequently polyadenylated, and a m7G 5' cap. The m7G has been removed or snatched. This product was derived from an intronless transcript.
Mature intronless

transcript derived

mRNA		R-NUL-158444 (Reactome) A mature mRNA that has been 3' cleaved, subsequently polyadenylated, and a m7G 5' cap. This product was derived from an intronless transcript.
NA ProteinP03468 (Uniprot-TrEMBL)
NA mRNA ProteinJ02146 (EMBL)
NAProteinP03468 (Uniprot-TrEMBL)
NCBP1 ProteinQ09161 (Uniprot-TrEMBL)
NCBP2 ProteinP52298 (Uniprot-TrEMBL)
NEP/NS2 ProteinP03508 (Uniprot-TrEMBL)
NEP/NS2ProteinP03508 (Uniprot-TrEMBL)
NFX.1 ProteinO43831 (Uniprot-TrEMBL)
NP ProteinP03466 (Uniprot-TrEMBL)
NP mRNA ProteinJ02147 (EMBL)
NP:Lipid RaftComplexR-FLU-195737 (Reactome)
NP:Lipid RaftComplexR-FLU-195766 (Reactome)
NPProteinP03466 (Uniprot-TrEMBL)
NS1 ProteinP03496 (Uniprot-TrEMBL)
NS1 mRNA ProteinJ02150 (EMBL)
NS1 mRNARnaJ02150 (EMBL)
NS1ProteinP03496 (Uniprot-TrEMBL)
NS2 mRNA ProteinJ02150 (EMBL)
NS2 mRNARnaJ02150 (EMBL)
NTPR-ALL-30595 (Reactome)
NUP107 ProteinP57740 (Uniprot-TrEMBL)
NUP133 ProteinQ8WUM0 (Uniprot-TrEMBL)
NUP153 ProteinP49790 (Uniprot-TrEMBL)
NUP155 ProteinO75694 (Uniprot-TrEMBL)
NUP160 ProteinQ12769 (Uniprot-TrEMBL)
NUP188 ProteinQ5SRE5 (Uniprot-TrEMBL)
NUP205 ProteinQ92621 (Uniprot-TrEMBL)
NUP210 ProteinQ8TEM1 (Uniprot-TrEMBL)
NUP214 ProteinP35658 (Uniprot-TrEMBL)
NUP35 ProteinQ8NFH5 (Uniprot-TrEMBL)
NUP37 ProteinQ8NFH4 (Uniprot-TrEMBL)
NUP43 ProteinQ8NFH3 (Uniprot-TrEMBL)
NUP50 ProteinQ9UKX7 (Uniprot-TrEMBL)
NUP54 ProteinQ7Z3B4 (Uniprot-TrEMBL)
NUP62 ProteinP37198 (Uniprot-TrEMBL)
NUP85 ProteinQ9BW27 (Uniprot-TrEMBL)
NUP88 ProteinQ99567 (Uniprot-TrEMBL)
NUP93 ProteinQ8N1F7 (Uniprot-TrEMBL)
NUP98-5 ProteinP52948-5 (Uniprot-TrEMBL)
NUPL1-2 ProteinQ9BVL2-1 (Uniprot-TrEMBL)
NUPL2 ProteinO15504 (Uniprot-TrEMBL)
Nuclear Pore Complex (NPC)ComplexR-HSA-157689 (Reactome)
Nup45 ProteinQ9BVL2-2 (Uniprot-TrEMBL)
P1 mRNA ProteinJ02151 (EMBL)
PA ProteinP03433 (Uniprot-TrEMBL)
PA mRNA ProteinV01106 (EMBL)
PAProteinP03433 (Uniprot-TrEMBL)
PB1 ProteinP03431 (Uniprot-TrEMBL)
PB1 mRNARnaJ02151 (EMBL)
PB1-F2ProteinP0C0U1 (Uniprot-TrEMBL)
PB1ProteinP03431 (Uniprot-TrEMBL)
PB2 ProteinP03428 (Uniprot-TrEMBL)
PB2ProteinP03428 (Uniprot-TrEMBL)
PCBP1 ProteinQ15365 (Uniprot-TrEMBL)
PCBP2 ProteinQ15366 (Uniprot-TrEMBL)
POLR2A ProteinP24928 (Uniprot-TrEMBL)
POLR2B ProteinP30876 (Uniprot-TrEMBL)
POLR2C ProteinP19387 (Uniprot-TrEMBL)
POLR2D ProteinO15514 (Uniprot-TrEMBL)
POLR2E ProteinP19388 (Uniprot-TrEMBL)
POLR2F ProteinP61218 (Uniprot-TrEMBL)
POLR2G ProteinP62487 (Uniprot-TrEMBL)
POLR2H ProteinP52434 (Uniprot-TrEMBL)
POLR2I ProteinP36954 (Uniprot-TrEMBL)
POLR2J ProteinP52435 (Uniprot-TrEMBL)
POLR2K ProteinP53803 (Uniprot-TrEMBL)
POLR2L ProteinP62875 (Uniprot-TrEMBL)
POM121 ProteinQ96HA1 (Uniprot-TrEMBL)
PTBP1 ProteinP26599 (Uniprot-TrEMBL)
PiMetaboliteCHEBI:18367 (ChEBI)
RAE1 ProteinP78406 (Uniprot-TrEMBL)
RAN ProteinP62826 (Uniprot-TrEMBL)
RANBP2 ProteinP49792 (Uniprot-TrEMBL)
RBM5 ProteinP52756 (Uniprot-TrEMBL)
RBMX ProteinP38159 (Uniprot-TrEMBL)
RNA

Polymerase II

(phosphorylated):TFIIF:capped pre-mRNA		ComplexR-HSA-113405 (Reactome)
RNP

Complex:Karyopherin

alpha		ComplexR-FLU-188871 (Reactome)
RNP pre-assembly complexComplexR-FLU-196496 (Reactome)
RNP:Karyopherin

alpha:Karyopherin

beta complex		ComplexR-FLU-188844 (Reactome)
RNP:Karyopherin

alpha:Karyopherin

beta complex		ComplexR-FLU-188853 (Reactome)
RNPS1 ProteinQ15287 (Uniprot-TrEMBL)
RPL10 ProteinP27635 (Uniprot-TrEMBL)
RPL10A ProteinP62906 (Uniprot-TrEMBL)
RPL11 ProteinP62913 (Uniprot-TrEMBL)
RPL12 ProteinP30050 (Uniprot-TrEMBL)
RPL13 ProteinP26373 (Uniprot-TrEMBL)
RPL13A ProteinP40429 (Uniprot-TrEMBL)
RPL14 ProteinP50914 (Uniprot-TrEMBL)
RPL15 ProteinP61313 (Uniprot-TrEMBL)
RPL17 ProteinP18621 (Uniprot-TrEMBL)
RPL18 ProteinQ07020 (Uniprot-TrEMBL)
RPL18A ProteinQ02543 (Uniprot-TrEMBL)
RPL19 ProteinP84098 (Uniprot-TrEMBL)
RPL21 ProteinP46778 (Uniprot-TrEMBL)
RPL22 ProteinP35268 (Uniprot-TrEMBL)
RPL23 ProteinP62829 (Uniprot-TrEMBL)
RPL23A ProteinP62750 (Uniprot-TrEMBL)
RPL24 ProteinP83731 (Uniprot-TrEMBL)
RPL26 ProteinP61254 (Uniprot-TrEMBL)
RPL26L1 ProteinQ9UNX3 (Uniprot-TrEMBL)
RPL27 ProteinP61353 (Uniprot-TrEMBL)
RPL27A ProteinP46776 (Uniprot-TrEMBL)
RPL28 ProteinP46779 (Uniprot-TrEMBL)
RPL29 ProteinP47914 (Uniprot-TrEMBL)
RPL3 ProteinP39023 (Uniprot-TrEMBL)
RPL30 ProteinP62888 (Uniprot-TrEMBL)
RPL31 ProteinP62899 (Uniprot-TrEMBL)
RPL32 ProteinP62910 (Uniprot-TrEMBL)
RPL34 ProteinP49207 (Uniprot-TrEMBL)
RPL35 ProteinP42766 (Uniprot-TrEMBL)
RPL35A ProteinP18077 (Uniprot-TrEMBL)
RPL36 ProteinQ9Y3U8 (Uniprot-TrEMBL)
RPL36A ProteinP83881 (Uniprot-TrEMBL)
RPL37 ProteinP61927 (Uniprot-TrEMBL)
RPL37A ProteinP61513 (Uniprot-TrEMBL)
RPL38 ProteinP63173 (Uniprot-TrEMBL)
RPL39 ProteinP62891 (Uniprot-TrEMBL)
RPL3L ProteinQ92901 (Uniprot-TrEMBL)
RPL4 ProteinP36578 (Uniprot-TrEMBL)
RPL40 ProteinP62987 (Uniprot-TrEMBL)
RPL41 ProteinP62945 (Uniprot-TrEMBL)
RPL5 ProteinP46777 (Uniprot-TrEMBL)
RPL6 ProteinQ02878 (Uniprot-TrEMBL)
RPL7 ProteinP18124 (Uniprot-TrEMBL)
RPL7A ProteinP62424 (Uniprot-TrEMBL)
RPL8 ProteinP62917 (Uniprot-TrEMBL)
RPL9 ProteinP32969 (Uniprot-TrEMBL)
RPLP0 ProteinP05388 (Uniprot-TrEMBL)
RPLP1 ProteinP05386 (Uniprot-TrEMBL)
RPLP2 ProteinP05387 (Uniprot-TrEMBL)
RPS10 ProteinP46783 (Uniprot-TrEMBL)
RPS11 ProteinP62280 (Uniprot-TrEMBL)
RPS12 ProteinP25398 (Uniprot-TrEMBL)
RPS13 ProteinP62277 (Uniprot-TrEMBL)
RPS14 ProteinP62263 (Uniprot-TrEMBL)
RPS15 ProteinP62841 (Uniprot-TrEMBL)
RPS15A ProteinP62244 (Uniprot-TrEMBL)
RPS16 ProteinP62249 (Uniprot-TrEMBL)
RPS17 ProteinP08708 (Uniprot-TrEMBL)
RPS18 ProteinP62269 (Uniprot-TrEMBL)
RPS19 ProteinP39019 (Uniprot-TrEMBL)
RPS2 ProteinP15880 (Uniprot-TrEMBL)
RPS20 ProteinP60866 (Uniprot-TrEMBL)
RPS21 ProteinP63220 (Uniprot-TrEMBL)
RPS23 ProteinP62266 (Uniprot-TrEMBL)
RPS24 ProteinP62847 (Uniprot-TrEMBL)
RPS25 ProteinP62851 (Uniprot-TrEMBL)
RPS26 ProteinP62854 (Uniprot-TrEMBL)
RPS27 ProteinP42677 (Uniprot-TrEMBL)
RPS27A(77-156) ProteinP62979 (Uniprot-TrEMBL)
RPS28 ProteinP62857 (Uniprot-TrEMBL)
RPS29 ProteinP62273 (Uniprot-TrEMBL)
RPS3 ProteinP23396 (Uniprot-TrEMBL)
RPS3A ProteinP61247 (Uniprot-TrEMBL)
RPS4X ProteinP62701 (Uniprot-TrEMBL)
RPS4Y1 ProteinP22090 (Uniprot-TrEMBL)
RPS5 ProteinP46782 (Uniprot-TrEMBL)
RPS6 ProteinP62753 (Uniprot-TrEMBL)
RPS7 ProteinP62081 (Uniprot-TrEMBL)
RPS8 ProteinP62241 (Uniprot-TrEMBL)
RPS9 ProteinP46781 (Uniprot-TrEMBL)
RPSA ProteinP08865 (Uniprot-TrEMBL)
Ran GTPase:GTPComplexR-HSA-165530 (Reactome)
Ribonucleoprotein (RNP) ComplexComplexR-FLU-188846 (Reactome)
Ribonucleoprotein (RNP) ComplexComplexR-FLU-188849 (Reactome)
SA MetaboliteCHEBI:26667 (ChEBI)
SAMetaboliteCHEBI:26667 (ChEBI)
SEH1L-2 ProteinQ96EE3-2 (Uniprot-TrEMBL)
SMC1A ProteinQ14683 (Uniprot-TrEMBL)
SNRNP70 ProteinP08621 (Uniprot-TrEMBL)
SNRPA ProteinP09012 (Uniprot-TrEMBL)
SNRPD2 ProteinP62316 (Uniprot-TrEMBL)
SNRPE ProteinP62304 (Uniprot-TrEMBL)
SNRPF ProteinP62306 (Uniprot-TrEMBL)
SNRPG ProteinP62308 (Uniprot-TrEMBL)
SRRM1 ProteinQ8IYB3 (Uniprot-TrEMBL)
SRSF1 ProteinQ07955 (Uniprot-TrEMBL)
SRSF2 ProteinQ01130 (Uniprot-TrEMBL)
SRSF3 ProteinP84103 (Uniprot-TrEMBL)
SRSF5 ProteinQ13243 (Uniprot-TrEMBL)
SRSF6 ProteinQ13247 (Uniprot-TrEMBL)
SRSF7 ProteinQ16629 (Uniprot-TrEMBL)
SRSF9 ProteinQ13242 (Uniprot-TrEMBL)
SUGP1 ProteinQ8IWZ8 (Uniprot-TrEMBL)
Segment 1 RNPComplexR-FLU-195947 (Reactome)
Segment 2 RNPComplexR-FLU-195950 (Reactome)
Segment 3 RNPComplexR-FLU-195952 (Reactome)
Segment 4 RNPComplexR-FLU-195942 (Reactome)
Segment 5 RNPComplexR-FLU-195951 (Reactome)
Segment 6 RNPComplexR-FLU-195943 (Reactome)
Segment 7 RNPComplexR-FLU-195939 (Reactome)
Segment 8 RNPComplexR-FLU-195949 (Reactome)
Sialic Acid Bound

Influenza A Viral

Particle		ComplexR-FLU-188954 (Reactome)
Sialic Acid Bound

Influenza A Viral

Particle		ComplexR-FLU-195945 (Reactome)
Spliceosomal E ComplexComplexR-HSA-72057 (Reactome)
TPR ProteinP12270 (Uniprot-TrEMBL)
U1 snRNA ProteinV00590 (EMBL)
U2AF1 ProteinQ01081 (Uniprot-TrEMBL)
U2AF2 ProteinP26368 (Uniprot-TrEMBL)
Viral PolymeraseComplexR-FLU-192720 (Reactome) Heterotrimeric influenza viral polymerase complex consisting of PB1, PB2, and PA; although capable of being imported into the nucleus independently, the three subunits of the influenza polymerase assemble in the nucleus to form a mature ternary polymerase complex that binds viral vRNA or cRNA (reviewed in Buolo et al., 2006).
Viral ProteinsComplexR-FLU-192631 (Reactome)
Viral ProteinsComplexR-FLU-2168084 (Reactome)
XPO1 ProteinO14980 (Uniprot-TrEMBL)
XPO1ProteinO14980 (Uniprot-TrEMBL)
YBX1 ProteinP67809 (Uniprot-TrEMBL)
cRNPComplexR-FLU-192682 (Reactome) Extended cRNA complexed with viral NP and trimeric polymerase.
p-S5-POLR2A ProteinP24928 (Uniprot-TrEMBL)
palmitylated M2 TetramerComplexR-FLU-195732 (Reactome)
palmitylated M2 TetramerComplexR-FLU-195761 (Reactome)
palmitylated M2 ProteinP06821 (Uniprot-TrEMBL)
vRNA (Genomic):NP ComplexComplexR-FLU-193302 (Reactome)
vRNA (genomic)R-FLU-192849 (Reactome)
vRNA Transcription ComplexComplexR-FLU-192703 (Reactome) The 5' and 3' ends of the vRNA bound to the PB1 subunit of the viral RNA polymerase; PB2 bound to the methylated cap on a host pre-mRNA amino acids (Cianci, 1995; Brownlee, 2002; Honda, 1999).
vRNP Export ComplexComplexR-HSA-192667 (Reactome)
vRNP destined for ExportComplexR-FLU-192922 (Reactome)
vRNP:M1 for ExportComplexR-FLU-192906 (Reactome)
vRNP:M1:NEP:NPComplexR-FLU-192768 (Reactome)
vRNP:M1:NEPComplexR-FLU-192767 (Reactome)
vRNPComplexR-FLU-192774 (Reactome) A three dimensional crystal structure of NP suggests that this molecule forms a trimer that binds viral RNA (Ye et al., 2006). Mutiple NP trimers complex vRNA or cRNA.
viral mRNAR-FLU-192803 (Reactome)
viral mRNAR-FLU-192988 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
80S ribosomemim-catalysisR-HSA-192704 (Reactome)
80S ribosomemim-catalysisR-HSA-192841 (Reactome)
Acidified Influenza

A Viral Particle Docked At The Endocytic Vesicle Membrane With An

Open Pore		ArrowR-HSA-168313 (Reactome)
Acidified Influenza

A Viral Particle Docked At The Endocytic Vesicle Membrane With An

Open Pore		R-HSA-168299 (Reactome)
Aminoacyl-tRNAR-HSA-192704 (Reactome)
Aminoacyl-tRNAR-HSA-192841 (Reactome)
CALRArrowR-HSA-169921 (Reactome)
CANXArrowR-HSA-169921 (Reactome)
ClathrinArrowR-HSA-168285 (Reactome)
Cleaved HA Influenza A Viral ParticleR-HSA-168272 (Reactome)
Crm1:Ran GTPase:GDPArrowR-HSA-168880 (Reactome)
DNAJC3ArrowR-HSA-192841 (Reactome)
Elongated vRNA-mRNA ComplexArrowR-HSA-168334 (Reactome)
Elongated vRNA-mRNA ComplexR-HSA-168301 (Reactome)
GRSF1ArrowR-HSA-192841 (Reactome)
Glycosylated NA TetramerArrowR-HSA-168869 (Reactome)
Glycosylated NA TetramerArrowR-HSA-168871 (Reactome)
Glycosylated NA TetramerArrowR-HSA-169847 (Reactome)
Glycosylated NA TetramerR-HSA-168869 (Reactome)
Glycosylated NA TetramerR-HSA-168871 (Reactome)
Glycosylated NA TetramerR-HSA-195726 (Reactome)
Glycosylated NAArrowR-HSA-169919 (Reactome)
Glycosylated NAR-HSA-169847 (Reactome)
Glycosylated and folded HA trimerArrowR-HSA-168869 (Reactome)
Glycosylated and folded HA trimerArrowR-HSA-168871 (Reactome)
Glycosylated and folded HA trimerArrowR-HSA-168875 (Reactome)
Glycosylated and folded HA trimerR-HSA-168858 (Reactome)
Glycosylated and folded HA trimerR-HSA-168869 (Reactome)
Glycosylated and folded HA trimerR-HSA-168871 (Reactome)
Glycosylated and folded HAArrowR-HSA-169921 (Reactome)
Glycosylated and folded HAR-HSA-168875 (Reactome)
Glycosylated,

palmitylated and folded HA trimer:Lipid Raft

Complex		ArrowR-HSA-168862 (Reactome)
Glycosylated,

palmitylated and folded HA trimer:Lipid Raft

Complex		ArrowR-HSA-195730 (Reactome)
Glycosylated,

palmitylated and folded HA trimer:Lipid Raft

Complex		R-HSA-195730 (Reactome)
Glycosylated,

palmitylated and

folded HA trimer		ArrowR-HSA-168858 (Reactome)
Glycosylated,

palmitylated and

folded HA trimer		R-HSA-168862 (Reactome)
Glycosylated,

palmitylated and

folded HA trimer		R-HSA-195926 (Reactome)
Gycosylated NA Tetramer:Lipid RaftArrowR-HSA-195726 (Reactome)
Gycosylated NA Tetramer:Lipid RaftArrowR-HSA-195730 (Reactome)
Gycosylated NA Tetramer:Lipid RaftR-HSA-195730 (Reactome)
Gycosylated NA TetramerR-HSA-195926 (Reactome)
H+ArrowR-HSA-168299 (Reactome)
H+R-HSA-168313 (Reactome)
HAArrowR-HSA-168884 (Reactome)
HAR-HSA-168884 (Reactome)
HAR-HSA-169921 (Reactome)
HSP90AA1ArrowR-HSA-192830 (Reactome)
HSPA1ATBarR-HSA-192746 (Reactome)
Host Derived Lipid

Bilayer Membrane Rich In Sphingolipids And

Cholesterol		R-HSA-168860 (Reactome)
IPO5ArrowR-HSA-192830 (Reactome)
Influenza A Viral

Envelope Inserted Into The Endocytic

Vesicle Membrane		ArrowR-HSA-168299 (Reactome)
Influenza A Viral

Particle Docked At The Endocytic Vesicle Membrane

With An Open Pore		ArrowR-HSA-168306 (Reactome)
Influenza A Viral

Particle Docked At The Endocytic Vesicle Membrane

With An Open Pore		R-HSA-168313 (Reactome)
Influenza A Viral

Particle Docked At The Endocytic Vesicle Membrane

With An Open Pore		mim-catalysisR-HSA-168313 (Reactome)
Influenza A Viral

Particle Docked At The Endocytic

Vesicle Membrane		ArrowR-HSA-168312 (Reactome)
Influenza A Viral

Particle Docked At The Endocytic

Vesicle Membrane		R-HSA-168306 (Reactome)
Influenza A Viral

Particle With A Fusion Competent

HA2		ArrowR-HSA-168324 (Reactome)
Influenza A Viral

Particle With A Fusion Competent

HA2		R-HSA-168312 (Reactome)
Influenza A Viral ParticleArrowR-HSA-168285 (Reactome)
Influenza A Viral ParticleArrowR-HSA-168870 (Reactome)
Influenza A Viral ParticleR-HSA-168324 (Reactome)
Influenza cRNA (complete)ArrowR-HSA-192851 (Reactome)
Initiated cRNA-vRNA ComplexArrowR-HSA-192916 (Reactome)
Initiated cRNA-vRNA ComplexR-HSA-192851 (Reactome)
Initiated vRNA

Transcription

Complex		ArrowR-HSA-168280 (Reactome)
Initiated vRNA

Transcription

Complex		R-HSA-168334 (Reactome)
Initiated vRNA-cRNA ComplexArrowR-HSA-192832 (Reactome)
Initiated vRNA-cRNA ComplexR-HSA-192624 (Reactome)
Intracellular assembly complexArrowR-HSA-195926 (Reactome)
Intracellular assembly complexR-HSA-168860 (Reactome)
KPNA1ArrowR-HSA-168310 (Reactome)
KPNA1R-HSA-168297 (Reactome)
KPNB1ArrowR-HSA-168310 (Reactome)
KPNB1R-HSA-168317 (Reactome)
Lipid RaftR-HSA-168862 (Reactome)
Lipid RaftR-HSA-168882 (Reactome)
Lipid RaftR-HSA-195726 (Reactome)
M1 mRNAR-HSA-192781 (Reactome)
M1ArrowR-HSA-168299 (Reactome)
M1ArrowR-HSA-168894 (Reactome)
M1R-HSA-168894 (Reactome)
M1R-HSA-192746 (Reactome)
M1R-HSA-195926 (Reactome)
M2 TetramerArrowR-HSA-168869 (Reactome)
M2 TetramerArrowR-HSA-168871 (Reactome)
M2 TetramerArrowR-HSA-188544 (Reactome)
M2 TetramerR-HSA-168869 (Reactome)
M2 TetramerR-HSA-168871 (Reactome)
M2 TetramerR-HSA-195739 (Reactome)
M2 mRNAArrowR-HSA-192781 (Reactome)
M2 mRNAArrowR-HSA-192925 (Reactome)
M2 mRNAR-HSA-192925 (Reactome)
M2ArrowR-HSA-195733 (Reactome)
M2R-HSA-188544 (Reactome)
M2R-HSA-195733 (Reactome)
Mature intronless

transcript derived mRNA with m7G cap

removed		ArrowR-HSA-168280 (Reactome)
Mature intronless

transcript derived

mRNA		R-HSA-168326 (Reactome)
NAArrowR-HSA-195734 (Reactome)
NAR-HSA-169919 (Reactome)
NAR-HSA-195734 (Reactome)
NAmim-catalysisR-HSA-168870 (Reactome)
NEP/NS2ArrowR-HSA-168299 (Reactome)
NEP/NS2R-HSA-168893 (Reactome)
NEP/NS2R-HSA-195926 (Reactome)
NP:Lipid RaftArrowR-HSA-168882 (Reactome)
NP:Lipid RaftArrowR-HSA-195730 (Reactome)
NP:Lipid RaftR-HSA-195730 (Reactome)
NPArrowR-HSA-168326 (Reactome)
NPArrowR-HSA-192677 (Reactome)
NPArrowR-HSA-192832 (Reactome)
NPR-HSA-168882 (Reactome)
NPR-HSA-192624 (Reactome)
NPR-HSA-192851 (Reactome)
NPR-HSA-192912 (Reactome)
NPR-HSA-195926 (Reactome)
NS1 mRNAR-HSA-192781 (Reactome)
NS1ArrowR-HSA-192841 (Reactome)
NS2 mRNAArrowR-HSA-192781 (Reactome)
NS2 mRNAArrowR-HSA-192925 (Reactome)
NS2 mRNAR-HSA-192925 (Reactome)
NTPR-HSA-168334 (Reactome)
NTPR-HSA-192624 (Reactome)
NTPR-HSA-192832 (Reactome)
NTPR-HSA-192851 (Reactome)
Nuclear Pore Complex (NPC)ArrowR-HSA-168337 (Reactome)
Nuclear Pore Complex (NPC)ArrowR-HSA-168880 (Reactome)
Nuclear Pore Complex (NPC)mim-catalysisR-HSA-192627 (Reactome)
Nuclear Pore Complex (NPC)mim-catalysisR-HSA-192925 (Reactome)
PAR-HSA-192677 (Reactome)
PAR-HSA-192830 (Reactome)
PAR-HSA-195926 (Reactome)
PB1 mRNAR-HSA-192704 (Reactome)
PB1-F2ArrowR-HSA-192704 (Reactome)
PB1R-HSA-192677 (Reactome)
PB1R-HSA-192830 (Reactome)
PB1R-HSA-195926 (Reactome)
PB2R-HSA-192677 (Reactome)
PB2R-HSA-192830 (Reactome)
PB2R-HSA-195926 (Reactome)
PiArrowR-HSA-168880 (Reactome)
R-HSA-168272 (Reactome) Influenza viruses bind via their surface HA (hemagglutinin) to sialic acid in alpha 2,3 or alpha 2,6 linkage with galactose on the host cell surface. Sialic acid in 2,6 linkages is characteristic of human cells while 2,3 linkages are characteristic of avian cells. The specificity of influenza HA for sialic acid in alpha 2,6 or alpha 2,3 linkages is a feature restricting the transfer of influenza viruses between avian species and humans. This species barrier can be overcome, however. Notably, passaged viruses adapt to their host through mutation in the receptor binding site of the viral HA gene.
R-HSA-168280 (Reactome) The host cell mRNA bound to viral RNA polymerase PB2 subunit is cleaved by the viral RNA polymerase PB1 subunit's endonuclease activity, and the capped 5' end plus 10-13 nucleotides of the host mRNA remains bound to the polymerase complex (Plotch, 1981; Krug, 1981; Hagen, 1994; Cianci, 1995, Li, 1998; Li, 2001). Viral mRNA may be protected against cap-snatching by the polymerase complex itself, which tightly binds capped viral mRNA (Shih, 1996). A guanine residue, complementary to a cytosine in the vRNA, is added to the host-derived cap, catalyzed by the RNA polymerase activity of the PB1 viral RNA polymerase subunit (Beaton, 1981; Toyoda, 1986).
R-HSA-168285 (Reactome) Virus particles bound to the cell surface can be internalized by four mechanisms. Most internalization appears to be mediated by clathrin-coated pits.
R-HSA-168297 (Reactome) The eight influenza virus genome segments never exist as naked RNA but are associated with four viral proteins to form viral ribonucleoprotein complexes (vRNPs). The major viral protein in the RNP complex is the nucleocapsid protein (NP), which coats the RNA. The remaining proteins PB1, PB2 and PA bind to the partially complementary ends of the viral RNA, creating the distinctive panhandle structure. The influenza viral NP behaves like a nuclear localization sequence (NLS) containing protein. The RNP docks at the nuclear envelope only in the presence of the heterodimeric karyopherin alpha and beta complex. Here karyopherin alpha recognizes the RNP.
R-HSA-168299 (Reactome) The influx of H+ ions into the virion disrupts protein-protein interactions, resulting in the release of the viral RNP from the viral matrix (M1) protein. The uncoating process is complete with the appearance of free RNP complexes in the cytosol.
R-HSA-168301 (Reactome) A poly-uridine sequence motif, consisting in most cases of 5-7 U residues, abuts the "panhandle" duplex structure in the vRNA; this sequence is approximately 16 nucleotides from the 5' end of this RNA duplex structure within the vRNA promoter. Encountering this signal, the viral RNA polymerase stutters, leading to the synthesis of a poly-A tail on the viral mRNA (Robertson, 1981; Luo, 1991; Li,1994; Poon, 1998; Zheng et al. 1999).
R-HSA-168306 (Reactome) The concerted structural change of several hemagglutinin molecules opens a pore through which the viral RNP will be able to pass into the host cell cytosol.
R-HSA-168310 (Reactome) Once the viral RNP and heterodimeric karyopherin complex has been transported into the nucleus the RNP dissasociates from the heterodimeric karyopherins.
R-HSA-168312 (Reactome) The fusion peptide of its HA2 subunit interacts with the endosome membrane. The transmembrane domain of the HA2 is inserted into the viral membrane and the fusion peptide is inserted into the endosomal membrane. In the acidic pH structure of HA the two ends of the HA complex are in juxtaposition.
R-HSA-168313 (Reactome) The uncoating of influenza viruses in endosomes is blocked by changes in pH caused by weak bases (e.g. ammonium chloride and chloroquine) or ionophores (e.g. monensin). Effective uncoating is also dependent on the presence of the viral M2 ion channel protein. Early on it was recognized that amantadine and rimantadine inhibit replication immediately following virus infection. Later it was found that the virus-associated M2 protein allows the influx of H+ ions from the endosome into the virion. This disrupts protein-protein interactions, resulting in the release of viral RNP free of the viral matrix (M1) protein. Amantadine and rimantadine have been shown to block the ion channel activity of the M2 protein and thus uncoating.
R-HSA-168317 (Reactome) The eight influenza virus genome segments are associated with four viral proteins to form viral ribonucleoprotein complexes (vRNPs). The major viral protein in the RNP complex is the nucleocapsid protein (NP), which coats the RNA. The remaining proteins PB1, PB2 and PA bind to the partially complementary ends of the viral RNA. The influenza viral NP behaves like a nuclear localization sequence (NLS) containing protein. The RNP docks at the nuclear envelope only in the presence of the heterodimeric karyopherin alpha and beta complex. Once the NLS is recognized by karyopherin alpha the karyopherin beta subunit joins the complex.
R-HSA-168324 (Reactome) The low pH of the endosome causes the viral HA (hemagglutinin) to undergo a structural change which frees the fusion peptide of its HA2 subunit.
R-HSA-168326 (Reactome) The 5' end of the vRNA associates with a binding site on the PB1 subunit of the viral RNA polymerase, distinct from the 3' vRNA binding site, which is subsequenty bound forming a loop. These binding events set off allosteric conformational changes in the trimeric polymerase complex that induce PB2 binding of the methylated cap on a host pre-mRNA (Plotch, 1981; Cianci, 1995; Li, 1998; Brownlee, 2002; Kolpashchikov, 2004). PB2 amino acids 242-282 and 538-577 are involved in cap binding (Honda, 1999). Direct or indirect interaction with active, transcribing host RNA polymerase II is thought to supply host mRNA for the caps (Bouloy, 1978; Engelhardt, 2005).
R-HSA-168334 (Reactome) Catalyzed by the RNA polymerase activity of the viral PB1 subunit, an mRNA complementary to the bound vRNA is synthesized (Plotch, 1977). PA and PB2 move down the growing mRNA in complex with PB1, with PB2 possibly dissociating from the cap (Braam, 1983). However, the 5’ end of the vRNA may remain bound during elongation as the template is threaded through in a 3’ to 5’ direction until a polyadenylation signal is encountered (Poon, 1998; Zheng, 1999).
R-HSA-168337 (Reactome) These RNPs (10-20nm wide) are too large to passively diffuse into the nucleus and therefore, once released from an incoming particle they must rely on the active import mechanism of the host cell nuclear pore complex (NPC). Once the RNP heterodimeric karyopherin complex docks at the NPC, it is transported into the nucleus.
R-HSA-168857 (Reactome) Virus NEP/NS2 interacts with human CRM1 (hCRM1), possibly dependent on a nuclear export signal (NES) motif in the NEP/NS2 N-terminal region (O'Neill, 1998; Neumann, 2000). The CRM1/exportin-1 pathway is a cellular mechanism for nuclear export, with CRM1 interacting with the Ran small GTPase and a cargo molecule's leucine-rich NES (Fukuda, 1997; Petosa, 2004). Leptomycin B, which specifically inhibits hCRM1, blocks export of viral RNP (Elton, 2001; Ma, 2001; Watanabe, 2001). Thus, NEP/NS2 interaction with cellular nuclear export machinery is essential for nuclear export of vRNP complexes and influenza virus release. A role for NP protein interaction with export machinery has also been proposed (Elton, 2001).
R-HSA-168858 (Reactome) The hemagglutinin of influenza virus is palmitoylated with long-chain fatty acids.
Palmitoylation of HA is believed to occur in the cis golgi network (Veit 1993), shortly after trimerisation of the molecule, and before cleavage of the HA into HA1 and HA2. HA is palmitoylated through thioester linkages at three cysteine residues located in the cytoplasmic domain and at the carboxy-terminal end of the transmembrane region. Lack of acylation has no obvious influence on the biological activities of HA.
R-HSA-168860 (Reactome) The final step in the budding process is the fusion of the lipid membrane surrounding the virion core, producing an extracellular enveloped virus particle.
R-HSA-168862 (Reactome) Influenza virus buds preferentially from lipid rafts (Scheiffele et al, 1999). NA protein individually accumulates at, and is selectively incorporated into rafts (Kundu et al., 1996). The signals for raft association lie within the transmembranse domain (TMD), (Barman et al., 2001, Barman et al., 2004), and raft association of NA has been shown to be essential for efficient virus replication. This is believed to be due to a requirement for a concentration of NA at specific areas of the plasma membrane to support a level of NA incorporation into budding particles sufficient to allow for efficient virus release (Barman et al., 2004).
R-HSA-168869 (Reactome) Viral proteins are packaged into a golgi apparatus bound transport vesicle.
R-HSA-168870 (Reactome) The release of influenza virus particles after seperation of the virus and infected cell membrane is an active process. During the budding process, HA on the surface of the newly budding virion binds to cell surface molecules containing sialic acid residues as seen during attachment. The NA glycoproteins neuraminidase activity is essential to cleave the link between the HA and sialic acid on the surface of the host cell from which the budding virus is emeging from. Thus the NA mediated cleavage of sialic acid residues terminally linked to glycoproteins and glycolipids is the final step in releasing the virus particle from the host cell. This essential role of NA in release of virus particle has been demonstrated with the use of NA inhibitors (Palese, 1976; Luo, 1999; Garman, 2004), ts NA mutant viruses (Palese, 1974) and with viruses lacking NA activity (Liu, 1995). In all cases, viruses remain bound to the cell surface in clumps in the absence of NA enzymatic activity, resulting in loss of infectivity. Addition of exogenous sialidase results in virus release and recovery of infectivity. The sialidase activity of the NA is also important for removing sialic acid from the HA on virus particles, if this is not removed, virus particles aggregate.
R-HSA-168871 (Reactome) Once the tranport vesicle arrives at the golgi apparatus, it docks and dumps its contents into the golgi lumen.
R-HSA-168875 (Reactome) Trimerisation of the fully folded and fully oxidised HA monomer is thought to occur in the endoplasmic reticulum and ERGIC compartment, following dissociation of HA from calnexin. Trimerisation is generally thought to be the final step in HA maturation occurring in the endoplasmic reticulum before transport to the Golgi apparatus, although Yewdell et al (1988) provide data suggesing that trimerisation may occur within the Golgi.
R-HSA-168880 (Reactome) Viral RNP, bound by M1 and NEP/NS2 interacting with CRM1, are shuttled through the nuclear pore into the cytoplasm (Martin, 1991; O'Neill, 1998; Buolo, 2006). This mechanism may resemble export of HIV-1 ribonucleoprotein, where the HIV-1 Rev export protein interacts with CRM1 (Askjaer, 1998). A number of cofactors are implicated in CRM1-mediated export, including the small GTPase Ran, Ran-binding proteins 1 and 3, and a guanine nucleotide exchange factor (Nilsson, 2001; Nemergut, 2002; Petosa, 2004). Ternary CRM1-cofactor-cargo complexes likely interact transiently with nuclear pore proteins (nucleoporins) as they traverse the pore (reviewed in Suntharalingam, 2003). RanGTP is hydrolyzed to RanGDP in the cytoplasm, an activity that can be stimulated by NEP/NS2 (Akarsu, 2003). Influenza infection activates Raf/MEK/ERK signaling, which is necessary for NEP/NS2-mediated export of viral RNP (Pleschka, 2001; Marjuki, 2006). Influenza vRNP complexes released into the cytoplasm do not re-enter the nucleus, as they are thought to remain bound by M1, preventing re-import (Martin, 1991). It has been suggested that M1 binding of zinc cations could distinguish M1 bound to the vRNP from polymerized, matrix M1 present in nascent virions (Elster, 1994).
R-HSA-168882 (Reactome) There is evidence that NP alone is intrinsically targeted to the apical plasma membrane and associates with lipid rafts in a cholesterol-dependent manner, which suggests that RNPs could reach the assembly site independently of the other viral components.
R-HSA-168884 (Reactome) The integral membrane protein HA is synthesized on membrane-bound ribosomes and subsequently transported across the endoplasmic reticulum, where it is folded, glycosylated, and assembled into a trimer.
R-HSA-168893 (Reactome) Structural characterization of NEP/NS2 suggests that acidic residues in the C-terminus of NEP/NS2 bind to M1, with Trp78 critical for interaction (Ward, 1995; Yasuda, 1993; Akarsu, 2003).
R-HSA-168894 (Reactome) There is evidence for the association of M1 with lipid rafts in influenza infected cells, whereas M1 expressed alone remains soluble (Ali et al., 2000; Zhang and Lamb, 1996), suggesting association of M1 with other viral proteins in targetting to the cell membrane. Coexpression of HA and NA together with M1 has been shown to promote raft association of M1. This association requires the TMD and cytoplasmic tails of HA and NA (Ali et al, 2000; Zhang et al, 2000). This is consistent with M1 becoming associated with HA and NA during their passage through the exocytic pathway to raft domains in the apical membrane. alternatively M1 may use the cytoskeleton to reach the virus assembly site, as M1 interacts with cytoskeletal components (Alvalos et al., 1997). The M1 interaction depends on the presence of RNP and is most likely mediated by direct binding of F-actin by NP (Digard et al., 1999).
R-HSA-168895 (Reactome) The random incorporation model as its name suggests proposes that there is no selection at all on which vRNPs are packaged. It is assumed that each vRNP has equal probability of being packaged, and that if enough vRNPS are packaged a particular percentage of budding virions will receive at least one copy of each genome segment. This model is supported by evidence that infectious virions may possess more than eight vRNPs assuring the presence of a full complement of eight vRNPs in a significant percentage of virus particles. Mathematical analysis of packaging suggested that twelve RNA segments would need to be packaged in order to obtain approximately 10% of virus particles that are fully infectious (Enami, 1991), a number that is compatible with experimental data (Donald, 1954). Due to the low amount of RNA per virion (estimated at 1-2% w/w), enumeration of the precise number of RNAs packaged in a virion is difficult.
R-HSA-169847 (Reactome) Tetramerisation of the NA occurs in the ER following an initial dimerisation step. Tetramerisation is believed to be dependant on glycosylation of the NA molecules
R-HSA-169919 (Reactome) Glycosylation of NA occurs within the endoplasmic reticulum and is believed to be neccessary for proper tetramerization of the NA dimers. Sugar residues become attached to four of the five potential glycosylation sites in the head of N1 neuraminidase (Hausman et al., 1997).
R-HSA-169921 (Reactome) The ectodomain of HA is translocated into the ER lumen, where it undergoes a series of folding events mediated by the formation of disulfide bonds and glycosylation reactions. The formation of a discrete intermediate species of highly folded monomeric protein preceeds trimerisation. The folding process is efficient and rapid, with greater than 90% of the protein trafficked to the golgi apparatus; and mature HA0 subunits appearing in a matter of a few minutes. Calnexin and calreticulin have been identified as cellular lectins which interact transiently with newly synthesized HA by attaching to partially trimmed N-linked oligosaccharides (Herbert et al., 1997), facilitating correct folding of the HA molecule.
R-HSA-188544 (Reactome) The M2 from influenza A virus is a 97-residue protein with a single transmembrane helix that associates to form a tetramer in the endoplasmic reticulum (Salom et al, 2000). A 15-20-residue segment C-terminal to the membrane-spanning region has been postulated to aid in the stabilization of the tetrameric assembly (Kochendoerfer et al 1999).
R-HSA-192624 (Reactome) Virion vRNP is capable of synthesizing cRNA immediately following entry into the cell nucleus (Vreede, 2006). The PB1 subunit principally catalyzes extension (Nakagawa, 1996). However, cRNA does not accumulate until later in the infection process, possiby requiring NP and the trimeric polymerase for stabilization (Vreede, 2004). The vRNA template is released.
R-HSA-192627 (Reactome) The viral polymerase complex produces positive-sense viral mRNA with host-cell derived 5' methyl caps. Capped viral mRNAs are selectively exported from the host cell nucleus through a currently unclear mechanism that may rely on components of the host cell mRNA export machinery (Chen, 2000; Engelhardt, 2006). Polyadenylation of viral mRNA appears be required for influenza mRNA export (Poon, 2000). A coupling of viral mRNA export with cellular pre-mRNA processing complexes, recruited by phosphorylation of host RNA polymerase II C-terminal domain which interacts with the viral polymerase (Engelhardt, 2005), has been proposed as controlling the export of a subset (M1, HA, and NS1, but not NP) of viral mRNA from the nucleus (Amorim, 2007).
R-HSA-192677 (Reactome) The nascent vRNP complexes, one for each gene segment, contain the negative-sense viral RNA and polymerase proteins (PB1, PB2, PA, and NP). In a model using negative-sense viral RNP reconstituted from transfected cells, there are multiple NP complexes and one polymerase complex arranged along a closed vRNA loop (Area et al., 2004). The three-dimensional structure of NP has revealed that three NP molecules form a stable trimer, interacting through beta-sheets b5, b6, and b7 in the C-terminal domain of the protein (Ye, 2006), with the viral RNA wrapping around the outside of the complex. Viral RNA from purified virions is present in an RNase-sensitive complex with NP and PB1, PB2, and PA, consistent with this structural model (Baudin et al, 1994; Ruigrok et al., 1995; Klumpp et al., 1997). It is not clear what controls the fate of vRNP, whether it is destined to become a template for transcription, for replication, or for export into the cytoplasm for packaging into virions at the plasma membrane, nor how distinct sub-nuclear localization and NP distribution at the nuclear matrix might mark, or polarize, a vRNP for export (Elton, 2005; Takizawa et al., 2006).
R-HSA-192704 (Reactome) For most influenza A strains (such as PR8), the PB1 mRNA segment produces a second protein, PB1-F2, from the +1 open reading frame (Chen, 2001). PB1-F2 is a pro-apoptotic, mitochondria-localized protein (Chen, 2001; Gibbs, 2003) that oligomerizes (Bruns, 2007) and sensitizes cells to death in concert with the mitochondrial ANT3 and VDAC proteins (Zamarin, 2005).
R-HSA-192746 (Reactome) M1 protein binds to viral RNP through its C-terminal domain (Baudin, 2001). The influenza M1 protein accumulates in the infected cell nucleus through a nuclear localization signal (NLS) RKLKR (residues 101-105) in its N-terminus (Ye, 1999). A host cell protein, HSP70, is thought to inhibit M1 binding at nonpermissive temperatures (Hirayama et al., 2004).
R-HSA-192781 (Reactome) The viral polymerase complex produces positive-sense viral mRNA with host-cell derived 5' methyl caps. Alternately spliced mRNA transcribed from M and NS vRNA segments 7 and 8, producing the spliced mRNA for M2 and NEP/NS2, respectively, are thought to be coupled to the cellular splicing and export mechanisms (Lamb, 1980; Lamb, 1981; Chen, 2000; Li, 2001). As segments 7 and 8 each encode two proteins, splicing must be regulated allowing for alternative mRNAs, with the spliced products in the minority (approximately 10%). M1 splicing may be regulated by the viral polymerase and the cellular SR splicing protein SF2/ASF (Shih, 1995; Shih, 1996); while NS1 splicing appears to be regulated by the viral mRNA intrinsically (Alonso-Caplen, 1991; Valcarel, 1991).
R-HSA-192830 (Reactome) The mature ternary influenza viral polymerase complex consists of PB1, PB2, and PA. The N-terminus of PB1 (residues 1-48) interacts with PB2, and amino acids 506-659 in PB1 interact with the PA subunit (Gonzalez, 1996; Perez, 2001). Although monomeric PB1, PB2 and PA, as well as PB1-PB2 and PB1-PA dimers are likely to exist in infected cells, it is believed that most of the polymerase proteins are assembled into the trimeric PB1-PB2-PA complex (Detjen, 1987). Newly synthesized subunits of the polymerase are imported into the nucleus through nuclear localization signals (NLS), which interact with cellular importin family proteins (Jones, 1986; Buolo, 2006). Importin beta-3 (Ran binding protein 5) facilitates nuclear import of PB1 and a PB1-PA dimer (Deng, 2006); coexpression of PA with PB1 was shown to enhance the import of PB1 (Fodor, 2004). A PB1-PB2 dimer has been found to interact with the molecular chaperone heat shock protein 90 (HSP90) to facilitate import (Naito, 2007). The three subunits assembled in the nucleus form a mature ternary polymerase complex that binds viral vRNA or cRNA (Jones, 1986; Buolo, 2006).
R-HSA-192832 (Reactome) Viral vRNA, complexed with NP protein, is bound by the trimeric viral polymerase complex in a stable secondary structure-dependent manner, referred to as a panhandle, fork or cork-screw (Fodor, 1994; Brownlee, 2002; Park, 2003; Crow, 2004). This RNA structure is made of both the 5’ and 3' ends of the vRNA. The polymerase is thought to first bind the 5' end of the vRNA and then the 3' end. Synthesis of cRNA initiates without a host cell methylated RNA cap as a primer (Beaton, 1986; Galarza, 1996; Deng, 2006; Engehardt, 2006).
R-HSA-192841 (Reactome) Spliced and unspliced viral mRNA exported into the cytoplasm are translated by the host cell ribosomal translation machinery (reviewed in Kash, 2006). At least ten viral proteins are synthesized: HA, NA, PB1, PB2, PA, NP, NS1, NEP/NS2 (from spliced NS mRNA), M1, and M2 (from spliced M mRNA). The abundance of each of these proteins is thought to be controlled by differential mRNA abundances and stability (Tekamp, 1980; Hatada, 1989). As the localization of the nascent polypeptides is different between viral proteins with transmembrane domains (HA, NA and M2, which translocate to the ER and are transported through the Golgi to the plasma membrane) and soluble viral proteins (such as NP, the polymerase subunits, and NS1), mechanisms linking the translation of particular viral mRNA with subsequent protein localization rely on signal sequences recognized by the cell.
R-HSA-192851 (Reactome) vRNA is synthesized from the complementary cRNA strand by the trimeric polymerase complex, and bound by free NP protein (Honda, 1988; Mikulasova, 2000; Neumann, 2004). The PB1 subunit, with PA, catalyzes extension (Nakagawa, 1996). The cRNA is released.
R-HSA-192912 (Reactome) Viral genomic RNA (vRNA) and complementary RNA (cRNA) are likely bound by the influenza nucleoprotein (NP) immediately upon synthesis. Although two nuclear localization signals have been mapped in the NP, an unconventional N-terminal NLS and a bipartite NLS within amino acids 198-216 (Wang, 1997; Neumann, 1997; Ozawa, 2007), the crystal structure of the NP suggests that only the unconventional NLS is exposed and can be used as a functional NLS (Ye, 2006). This unconvenetional NLS interacts with importins alpha-1 and -2 (Cros et al., 2005; Wang et al., 1997; Buolo et al., 2006). The three-dimensional structure of NP has revealed that NP molecules associate as a trimer, interacting through beta-sheets b5, b6, and b7 in the C-terminal domain of the protein; the viral RNA likely wraps around the outside of the complex (Ye, 2006).
R-HSA-192916 (Reactome) Initiation of synthesis of the viral genomic RNA (vRNA) is thought to require hairpin (or panhandle/corkscrew) RNA loop structures formed by both the 5' and 3' ends of the cRNA (Pritlove, 1995; Crow, 2004; Park, 2003; Deng, 2006). The cRNA promoter has a similar structure to the vRNA promoter, but slight sequence differences are believed to result in a stronger cRNA promoter. As with the vRNA promoter, the polymerase is thought to first bind to the 5' end of the cRNA, then to the 3' end, and subsequently initiate RNA synthesis.
R-HSA-192925 (Reactome) In the cases of spliced, polyadenylated mRNA transcribed from M (segment 7) and NS (segment 8) vRNA templates (producing the spliced mRNA for M2 and NS2/NEP, respectively), export may be coupled to aspects of the cellular splicing and export mechanisms (Chen, 2000; Alonso-Caplan et al, 1992; Amorim, 2006). Simultaneously, the export of cellular mRNA appear to be inhibited by the viral NS1 protein, which binds to the cellular cleavage and polyadenylation specificity factor (CPSF), preventing polyadenylation and completion of pre-mRNA processing (Nemerof et al., 1998; Fortes, 1994; Lu, 1994; Li, 2001).
R-HSA-195726 (Reactome) Influenza virus buds preferentially from lipid rafts (Scheiffele et al, 1999). NA protein individually accumulates at, and is selectively incorporated into rafts (Kundu et al., 1996). The signals for raft association lie within the transmembranse domain (TMD), (Barman et al., 2001, Barman et al., 2004), and raft association of NA has been shown to be essential for efficient virus replication. This is believed to be due to a requirement for a concentration of NA at specific areas of the plasma membrane to support a level of NA incorporation into budding particles sufficient to allow for efficient virus release (Barman et al., 2004).
R-HSA-195730 (Reactome) Once processed, the viral proteins are transported from the golgi apparatus to the plasma membrane.
R-HSA-195733 (Reactome) The integral membrane protein M2 is synthesized on membrane-bound ribosomes and subsequently transported across the ER, where it is folded and assembled into a tetramer.
R-HSA-195734 (Reactome) The integral membrane protein NA is synthesized on membrane-bound ribosomes and subsequently transported across the ER where it is folded and glycosylated. Subsequently NA is assembled into a tetramer.
R-HSA-195739 (Reactome) Palmitoylation of influenza A M2 occurs in the ER, or cis golgi network, following tetramerisation. The palmitoylation reaction proceeds via a labile thioester type bond at a specific residue of M2 (Sugrue et al., 1990).
R-HSA-195926 (Reactome) As influenza viruses bud from the plasma membrane of infected cells, complete virions are not seen inside cells. In polarized epithelial cells, assembly and budding of influenza occurs from the apical plasma membrane (Schmitt, 2004). For efficient assembly, all virion components must accumulate at the budding site, and it is believed that the viral glycoprotein accumulation determines the site of virus assembly and budding (Nayak, 2004). M1 is thought to be the bridge between the envelope glycoproteins and the RNPs for assembly (Schmitt, 2004). M2 is also required, because if it is not present RNPs are not packaged into budding virions (McCown, 2005), however it role is not known.
RNA

Polymerase II

(phosphorylated):TFIIF:capped pre-mRNA		ArrowR-HSA-168326 (Reactome)
RNP

Complex:Karyopherin

alpha		ArrowR-HSA-168297 (Reactome)
RNP

Complex:Karyopherin

alpha		R-HSA-168317 (Reactome)
RNP pre-assembly complexArrowR-HSA-168895 (Reactome)
RNP pre-assembly complexR-HSA-195926 (Reactome)
RNP:Karyopherin

alpha:Karyopherin

beta complex		ArrowR-HSA-168317 (Reactome)
RNP:Karyopherin

alpha:Karyopherin

beta complex		ArrowR-HSA-168337 (Reactome)
RNP:Karyopherin

alpha:Karyopherin

beta complex		R-HSA-168310 (Reactome)
RNP:Karyopherin

alpha:Karyopherin

beta complex		R-HSA-168337 (Reactome)
Ran GTPase:GTPR-HSA-168880 (Reactome)
Ribonucleoprotein (RNP) ComplexArrowR-HSA-168299 (Reactome)
Ribonucleoprotein (RNP) ComplexArrowR-HSA-168310 (Reactome)
Ribonucleoprotein (RNP) ComplexR-HSA-168297 (Reactome)
SAArrowR-HSA-168285 (Reactome)
SAR-HSA-168272 (Reactome)
SAR-HSA-168860 (Reactome)
Segment 1 RNPR-HSA-168895 (Reactome)
Segment 2 RNPR-HSA-168895 (Reactome)
Segment 3 RNPR-HSA-168895 (Reactome)
Segment 4 RNPR-HSA-168895 (Reactome)
Segment 5 RNPR-HSA-168895 (Reactome)
Segment 6 RNPR-HSA-168895 (Reactome)
Segment 7 RNPR-HSA-168895 (Reactome)
Segment 8 RNPR-HSA-168895 (Reactome)
Sialic Acid Bound

Influenza A Viral

Particle		ArrowR-HSA-168272 (Reactome)
Sialic Acid Bound

Influenza A Viral

Particle		ArrowR-HSA-168860 (Reactome)
Sialic Acid Bound

Influenza A Viral

Particle		R-HSA-168285 (Reactome)
Sialic Acid Bound

Influenza A Viral

Particle		R-HSA-168870 (Reactome)
Viral PolymeraseArrowR-HSA-168301 (Reactome)
Viral PolymeraseArrowR-HSA-192624 (Reactome)
Viral PolymeraseArrowR-HSA-192830 (Reactome)
Viral PolymeraseArrowR-HSA-192851 (Reactome)
Viral PolymeraseR-HSA-168326 (Reactome)
Viral PolymeraseR-HSA-192832 (Reactome)
Viral PolymeraseR-HSA-192916 (Reactome)
Viral Polymerasemim-catalysisR-HSA-168280 (Reactome)
Viral Polymerasemim-catalysisR-HSA-168301 (Reactome)
Viral Polymerasemim-catalysisR-HSA-168334 (Reactome)
Viral Polymerasemim-catalysisR-HSA-192624 (Reactome)
Viral Polymerasemim-catalysisR-HSA-192832 (Reactome)
Viral Polymerasemim-catalysisR-HSA-192851 (Reactome)
Viral Polymerasemim-catalysisR-HSA-192916 (Reactome)
Viral ProteinsArrowR-HSA-192841 (Reactome)
XPO1R-HSA-168857 (Reactome)
cRNPArrowR-HSA-192624 (Reactome)
cRNPArrowR-HSA-192851 (Reactome)
cRNPR-HSA-192916 (Reactome)
palmitylated M2 TetramerArrowR-HSA-195730 (Reactome)
palmitylated M2 TetramerArrowR-HSA-195739 (Reactome)
palmitylated M2 TetramerR-HSA-195730 (Reactome)
palmitylated M2 TetramerR-HSA-195926 (Reactome)
vRNA (Genomic):NP ComplexArrowR-HSA-168301 (Reactome)
vRNA (Genomic):NP ComplexArrowR-HSA-192624 (Reactome)
vRNA (Genomic):NP ComplexArrowR-HSA-192851 (Reactome)
vRNA (Genomic):NP ComplexArrowR-HSA-192912 (Reactome)
vRNA (Genomic):NP ComplexR-HSA-168326 (Reactome)
vRNA (Genomic):NP ComplexR-HSA-192832 (Reactome)
vRNA (genomic)R-HSA-192912 (Reactome)
vRNA Transcription ComplexArrowR-HSA-168326 (Reactome)
vRNA Transcription ComplexR-HSA-168280 (Reactome)
vRNP Export ComplexArrowR-HSA-168857 (Reactome)
vRNP Export ComplexR-HSA-168880 (Reactome)
vRNP destined for ExportArrowR-HSA-192677 (Reactome)
vRNP destined for ExportR-HSA-192746 (Reactome)
vRNP:M1 for ExportArrowR-HSA-192746 (Reactome)
vRNP:M1 for ExportR-HSA-168893 (Reactome)
vRNP:M1:NEP:NPArrowR-HSA-168880 (Reactome)
vRNP:M1:NEPArrowR-HSA-168893 (Reactome)
vRNP:M1:NEPR-HSA-168857 (Reactome)
vRNPR-HSA-192677 (Reactome)
viral mRNAArrowR-HSA-168301 (Reactome)
viral mRNAArrowR-HSA-192627 (Reactome)
viral mRNAR-HSA-192627 (Reactome)
viral mRNAR-HSA-192841 (Reactome)

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