Ebola virus infection in host (Homo sapiens)

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The Ebola virus (EBOV) pathway represents the virus infection on humans, depicted from the left to the right of the picture. The initial targets are macrophages and dendritic cells, but the virus has tropism to infect all kinds of cells, with the exception of lymphocytes. Here we represent all cells in general within one diagram.

Ebola attaches to the plasma membrane and after that, a viral glycoprotein induces penetration by endocytosis. This process is made by membrane proteins. During the penetration, its particles travel in compartments where viral glycoproteins are cleaved and fused to the endosomal membrane, which results in the uncoating of viral particles into the cell's cytoplasm. The virus then begins replicating and down-regulating the host's immune response. During the release process, the newly-created viruses are released from host cells, either by causing them to break apart, by waiting for their death, or by budding off through their membrane. Depending on the type of infected cell some trans-infection could happen.

This pathway was built using a text-mining approach to obtain interactions between genes related to this process. To our knowledge, it is the first comprehensive pathway depicting the Ebola pathway to date.

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  1. Feng Z, Cerveny M, Yan Z, He B; ''The VP35 protein of Ebola virus inhibits the antiviral effect mediated by double-stranded RNA-dependent protein kinase PKR.''; J Virol, 2007 PubMed Europe PMC Scholia
  2. Bhattacharyya S, Hope TJ, Young JA; ''Differential requirements for clathrin endocytic pathway components in cellular entry by Ebola and Marburg glycoprotein pseudovirions.''; Virology, 2011 PubMed Europe PMC Scholia
  3. Yan H, Kamiya T, Suabjakyong P, Tsuji NM; ''Targeting C-Type Lectin Receptors for Cancer Immunity.''; Front Immunol, 2015 PubMed Europe PMC Scholia
  4. Audet J, Kobinger GP; ''Immune evasion in ebolavirus infections.''; Viral Immunol, 2015 PubMed Europe PMC Scholia
  5. Luthra P, Jordan DS, Leung DW, Amarasinghe GK, Basler CF; ''Ebola virus VP35 interaction with dynein LC8 regulates viral RNA synthesis.''; J Virol, 2015 PubMed Europe PMC Scholia
  6. Luthra P, Ramanan P, Mire CE, Weisend C, Tsuda Y, Yen B, Liu G, Leung DW, Geisbert TW, Ebihara H, Amarasinghe GK, Basler CF; ''Mutual antagonism between the Ebola virus VP35 protein and the RIG-I activator PACT determines infection outcome.''; Cell Host Microbe, 2013 PubMed Europe PMC Scholia
  7. Lu J, Qu Y, Liu Y, Jambusaria R, Han Z, Ruthel G, Freedman BD, Harty RN; ''Host IQGAP1 and Ebola virus VP40 interactions facilitate virus-like particle egress.''; J Virol, 2013 PubMed Europe PMC Scholia
  8. Lennemann NJ, Rhein BA, Ndungo E, Chandran K, Qiu X, Maury W; ''Comprehensive functional analysis of N-linked glycans on Ebola virus GP1.''; MBio, 2014 PubMed Europe PMC Scholia
  9. Li M, Ablan SD, Miao C, Zheng YM, Fuller MS, Rennert PD, Maury W, Johnson MC, Freed EO, Liu SL; ''TIM-family proteins inhibit HIV-1 release.''; Proc Natl Acad Sci U S A, 2014 PubMed Europe PMC Scholia
  10. Mason CP, Tarr AW; ''Human lectins and their roles in viral infections.''; Molecules, 2015 PubMed Europe PMC Scholia
  11. Basler CF, Amarasinghe GK; ''Evasion of interferon responses by Ebola and Marburg viruses.''; J Interferon Cytokine Res, 2009 PubMed Europe PMC Scholia
  12. Melanson VR, Kalina WV, Williams P; ''Ebola virus infection induces irregular dendritic cell gene expression.''; Viral Immunol, 2015 PubMed Europe PMC Scholia
  13. Reid SP, Leung LW, Hartman AL, Martinez O, Shaw ML, Carbonnelle C, Volchkov VE, Nichol ST, Basler CF; ''Ebola virus VP24 binds karyopherin alpha1 and blocks STAT1 nuclear accumulation.''; J Virol, 2006 PubMed Europe PMC Scholia
  14. Chan SY, Empig CJ, Welte FJ, Speck RF, Schmaljohn A, Kreisberg JF, Goldsmith MA; ''Folate receptor-alpha is a cofactor for cellular entry by Marburg and Ebola viruses.''; Cell, 2001 PubMed Europe PMC Scholia
  15. Murray JL, Mavrakis M, McDonald NJ, Yilla M, Sheng J, Bellini WJ, Zhao L, Le Doux JM, Shaw MW, Luo CC, Lippincott-Schwartz J, Sanchez A, Rubin DH, Hodge TW; ''Rab9 GTPase is required for replication of human immunodeficiency virus type 1, filoviruses, and measles virus.''; J Virol, 2005 PubMed Europe PMC Scholia
  16. Esteves GH, Simoes AC, Souza E, Dias RA, Ospina R, Venancio TM; ''New insights about host response to smallpox using microarray data.''; BMC Syst Biol, 2007 PubMed Europe PMC Scholia
  17. Vande Burgt NH, Kaletsky RL, Bates P; ''Requirements within the Ebola Viral Glycoprotein for Tetherin Antagonism.''; Viruses, 2015 PubMed Europe PMC Scholia
  18. Prins KC, Cardenas WB, Basler CF; ''Ebola virus protein VP35 impairs the function of interferon regulatory factor-activating kinases IKKepsilon and TBK-1.''; J Virol, 2009 PubMed Europe PMC Scholia
  19. Geijtenbeek TB, Krooshoop DJ, Bleijs DA, van Vliet SJ, van Duijnhoven GC, Grabovsky V, Alon R, Figdor CG, van Kooyk Y; ''DC-SIGN-ICAM-2 interaction mediates dendritic cell trafficking.''; Nat Immunol, 2000 PubMed Europe PMC Scholia
  20. Brecher M, Schornberg KL, Delos SE, Fusco ML, Saphire EO, White JM; ''Cathepsin cleavage potentiates the Ebola virus glycoprotein to undergo a subsequent fusion-relevant conformational change.''; J Virol, 2012 PubMed Europe PMC Scholia
  21. Saeed MF, Kolokoltsov AA, Freiberg AN, Holbrook MR, Davey RA; ''Phosphoinositide-3 kinase-Akt pathway controls cellular entry of Ebola virus''; , 2008 PubMed Europe PMC Scholia
  22. Wang H, Shi Y, Song J, Qi J, Lu G, Yan J, Gao GF; ''Ebola Viral Glycoprotein Bound to Its Endosomal Receptor Niemann-Pick C1.''; Cell, 2016 PubMed Europe PMC Scholia
  23. Okumura A, Rasmussen AL, Halfmann P, Feldmann F, Yoshimura A, Feldmann H, Kawaoka Y, Harty RN, Katze MG; ''Suppressor of Cytokine Signaling 3 Is an Inducible Host Factor That Regulates Virus Egress during Ebola Virus Infection.''; J Virol, 2015 PubMed Europe PMC Scholia
  24. Brudner M, Karpel M, Lear C, Chen L, Yantosca LM, Scully C, Sarraju A, Sokolovska A, Zariffard MR, Eisen DP, Mungall BA, Kotton DN, Omari A, Huang IC, Farzan M, Takahashi K, Stuart L, Stahl GL, Ezekowitz AB, Spear GT, Olinger GG, Schmidt EV, Michelow IC; ''Lectin-dependent enhancement of Ebola virus infection via soluble and transmembrane C-type lectin receptors.''; PLoS One, 2013 PubMed Europe PMC Scholia
  25. Panchal RG, Ruthel G, Kenny TA, Kallstrom GH, Lane D, Badie SS, Li L, Bavari S, Aman MJ; ''In vivo oligomerization and raft localization of Ebola virus protein VP40 during vesicular budding.''; Proc Natl Acad Sci U S A, 2003 PubMed Europe PMC Scholia
  26. Quinn K, Brindley MA, Weller ML, Kaludov N, Kondratowicz A, Hunt CL, Sinn PL, McCray PB Jr, Stein CS, Davidson BL, Flick R, Mandell R, Staplin W, Maury W, Chiorini JA; ''Rho GTPases modulate entry of Ebola virus and vesicular stomatitis virus pseudotyped vectors.''; J Virol, 2009 PubMed Europe PMC Scholia
  27. Morizono K, Chen IS; ''Role of phosphatidylserine receptors in enveloped virus infection.''; J Virol, 2014 PubMed Europe PMC Scholia
  28. Gramberg T, Hofmann H, Moller P, Lalor PF, Marzi A, Geier M, Krumbiegel M, Winkler T, Kirchhoff F, Adams DH, Becker S, Munch J, Pohlmann S; ''LSECtin interacts with filovirus glycoproteins and the spike protein of SARS coronavirus.''; Virology, 2005 PubMed Europe PMC Scholia
  29. Dolnik O, Volchkova V, Garten W, Carbonnelle C, Becker S, Kahnt J, Stroher U, Klenk HD, Volchkov V; ''Ectodomain shedding of the glycoprotein GP of Ebola virus.''; EMBO J, 2004 PubMed Europe PMC Scholia
  30. Jemielity S, Wang JJ, Chan YK, Ahmed AA, Li W, Monahan S, Bu X, Farzan M, Freeman GJ, Umetsu DT, Dekruyff RH, Choe H; ''TIM-family proteins promote infection of multiple enveloped viruses through virion-associated phosphatidylserine.''; PLoS Pathog, 2013 PubMed Europe PMC Scholia
  31. Yuan S, Cao L, Ling H, Dang M, Sun Y, Zhang X, Chen Y, Zhang L, Su D, Wang X, Rao Z; ''TIM-1 acts a dual-attachment receptor for Ebolavirus by interacting directly with viral GP and the PS on the viral envelope.''; Protein Cell, 2015 PubMed Europe PMC Scholia
  32. Bhattacharyya S, Mulherkar N, Chandran K; ''Endocytic pathways involved in filovirus entry: advances, implications and future directions.''; Viruses, 2012 PubMed Europe PMC Scholia
  33. Spence JS, Krause TB, Mittler E, Jangra RK, Chandran K; ''Direct Visualization of Ebola Virus Fusion Triggering in the Endocytic Pathway.''; MBio, 2016 PubMed Europe PMC Scholia
  34. Shimojima M, Takada A, Ebihara H, Neumann G, Fujioka K, Irimura T, Jones S, Feldmann H, Kawaoka Y; ''Tyro3 family-mediated cell entry of Ebola and Marburg viruses.''; J Virol, 2006 PubMed Europe PMC Scholia
  35. Carette JE, Raaben M, Wong AC, Herbert AS, Obernosterer G, Mulherkar N, Kuehne AI, Kranzusch PJ, Griffin AM, Ruthel G, Dal Cin P, Dye JM, Whelan SP, Chandran K, Brummelkamp TR; ''Ebola virus entry requires the cholesterol transporter Niemann-Pick C1.''; Nature, 2011 PubMed Europe PMC Scholia
  36. Dominguez-Soto A, Aragoneses-Fenoll L, Martin-Gayo E, Martinez-Prats L, Colmenares M, Naranjo-Gomez M, Borras FE, Munoz P, Zubiaur M, Toribio ML, Delgado R, Corbi AL; ''The DC-SIGN-related lectin LSECtin mediates antigen capture and pathogen binding by human myeloid cells.''; Blood, 2007 PubMed Europe PMC Scholia
  37. Zhang AP, Bornholdt ZA, Liu T, Abelson DM, Lee DE, Li S, Woods VL Jr, Saphire EO; ''The ebola virus interferon antagonist VP24 directly binds STAT1 and has a novel, pyramidal fold.''; PLoS Pathog, 2012 PubMed Europe PMC Scholia
  38. Garrett WS, Chen LM, Kroschewski R, Ebersold M, Turley S, Trombetta S, Galan JE, Mellman I.; ''Developmental control of endocytosis in dendritic cells by Cdc42.''; Cell, 2000 PubMed Europe PMC Scholia
  39. Simmons JA, D'Souza RS, Ruas M, Galione A, Casanova JE, White JM; ''Ebolavirus Glycoprotein Directs Fusion through NPC1+ Endolysosomes.''; J Virol, 2016 PubMed Europe PMC Scholia


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120623view22:45, 20 December 2021KhanspersModified title
118435view14:40, 27 May 2021Mkutmonfixed publication refs
117706view12:26, 22 May 2021EweitzModified title
101851view14:32, 13 November 2018Elisson nl
101850view14:30, 13 November 2018Elisson nlInteractions correction
98605view20:09, 20 September 2018Elisson nlModified description
98604view19:52, 20 September 2018Elisson nlModified description
98603view19:48, 20 September 2018Elisson nlModification in interactions
98602view19:09, 20 September 2018Elisson nlAnnotated interaction
98332view04:31, 23 August 2018Elisson nlModified description
98331view04:08, 23 August 2018Elisson nlReferences Accentuation Correction
98330view03:54, 23 August 2018Elisson nlReferences Changed
98292view15:35, 16 August 2018DeSlAdded last missing IDs, coloured MHC1 and 2 subunits for clarity 9couldn't find a ID for these groups). Also added a lit. reference describing the effect of LC8 on VP35
98291view15:17, 16 August 2018DeSlAdded more identifiers.
98290view14:57, 16 August 2018DeSlModified description
97372view19:31, 11 May 2018Elisson nlNew References
97362view20:19, 10 May 2018Elisson nlReferences
97361view19:57, 10 May 2018Elisson nlReferences
97360view19:37, 10 May 2018Elisson nlReferences
97357view19:15, 10 May 2018Elisson nlReferences
97356view19:12, 10 May 2018Elisson nlReferences
97353view19:00, 10 May 2018Elisson nlReferences
97351view18:55, 10 May 2018Elisson nlNew References
97327view19:23, 9 May 2018KhanspersOntology Term : 'viral infectious disease' added !
97326view19:22, 9 May 2018KhanspersOntology Term : 'Ebola hemorrhagic fever' added !
97325view19:22, 9 May 2018Khanspersadded xrefs
97170view21:45, 2 May 2018Elisson nlReferences
96845view17:45, 12 April 2018Elisson nlModified description
96805view10:25, 9 April 2018DeSlChanged lines to graphical lines for Ebola virus drawing
96804view10:17, 9 April 2018DeSlAdded IDs from https://www.wikipathways.org/index.php/Pathway:WP4180
96119view02:55, 20 February 2018Elisson nlModified description
96118view02:47, 20 February 2018Elisson nlNew pathway

External references


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NameTypeDatabase referenceComment
ACTBGeneProductENSG00000075624 (Ensembl)
ACTG1GeneProductENSG00000184009 (Ensembl)
ACTINGeneProductIPR004000 (InterPro)
ACTN1GeneProductENSG00000072110 (Ensembl)
ACTN4GeneProductENSG00000130402 (Ensembl)
ADAM17GeneProductENSG00000151694 (Ensembl)
AKT1GeneProductENSG00000142208 (Ensembl)
ASGR1GeneProductENSG00000141505 (Ensembl)
AXLGeneProductENSG00000167601 (Ensembl)
BST2GeneProductENSG00000130303 (Ensembl)
C1QBPGeneProductENSG00000108561 (Ensembl)
CAV1GeneProductENSG00000105974 (Ensembl)
CAV2GeneProductENSG00000105971 (Ensembl)
CAV3GeneProductENSG00000182533 (Ensembl)
CAVEOLINGeneProductIPR001612 (InterPro)
CD209GeneProductENSG00000090659 (Ensembl)
CD300AGeneProductENSG00000167851 (Ensembl)
CDC42GeneProductENSG00000070831 (Ensembl)
CDC44GeneProductP35251 (Uniprot-TrEMBL) Annotated according to synonimic name with RFC1 according to Uniprot (although not mentioned for Homo sapiens species).
CLATHRINGeneProduct1211 (Entrez Gene)
CLEC10AGeneProductENSG00000132514 (Ensembl)
CLEC4GGeneProductENSG00000182566 (Ensembl)
CLEC4MGeneProductENSG00000104938 (Ensembl)
CLEC6AGeneProductENSG00000205846 (Ensembl)
CLTAGeneProductENSG00000122705 (Ensembl)
CLTBGeneProductENSG00000175416 (Ensembl)
CLTCGeneProductENSG00000141367 (Ensembl)
CLTCL1GeneProductENSG00000070371 (Ensembl)
CREBBPGeneProductENSG00000005339 (Ensembl)
CTSBGeneProductENSG00000164733 (Ensembl)
CTSLGeneProductENSG00000135047 (Ensembl)
DAB2IPGeneProductENSG00000136848 (Ensembl)
DDX58GeneProductENSG00000107201 (Ensembl)
EGFRGeneProductENSG00000146648 (Ensembl)
EIF2AK2GeneProductENSG00000055332 (Ensembl)
EIF2S1GeneProductENSG00000134001 (Ensembl)
EP300GeneProductENSG00000100393 (Ensembl)
EPS15GeneProductENSG00000085832 (Ensembl)
F-ACTINGeneProductENSG00000075624 (Ensembl)
FLNAGeneProductENSG00000196924 (Ensembl)
FLNBGeneProductENSG00000136068 (Ensembl)
FLNCGeneProductENSG00000128591 (Ensembl)
FOLR1GeneProductENSG00000110195 (Ensembl)
Filamin AGeneProduct2316 (Entrez Gene)
Filamin BGeneProduct2317 (Entrez Gene)
Filamin CGeneProduct2318 (Entrez Gene)
GAS6GeneProductENSG00000183087 (Ensembl)
GELSOLINGeneProductA0A0A0MS51 (Uniprot-TrEMBL)
GSNGeneProductENSG00000148180 (Ensembl)
HAVCR1GeneProductENSG00000113249 (Ensembl)
HAVCR2GeneProductENSG00000135077 (Ensembl)
HLA-AGeneProductENSG00000206503 (Ensembl)
HLA-BGeneProductENSG00000234745 (Ensembl)
HLA-CGeneProductENSG00000204525 (Ensembl)
HLA-DMAGeneProductENSG00000204257 (Ensembl)
HLA-DMBGeneProductENSG00000242574 (Ensembl)
HLA-DOAGeneProductENSG00000204252 (Ensembl)
HLA-DOBGeneProductENSG00000241106 (Ensembl)
HLA-DPA1GeneProductENSG00000231389 (Ensembl)
HLA-DPB1GeneProductENSG00000223865 (Ensembl)
HLA-DQA1GeneProductENSG00000196735 (Ensembl)
HLA-DQA2GeneProductENSG00000237541 (Ensembl)
HLA-DQB1GeneProductENSG00000179344 (Ensembl)
HLA-DQB2GeneProductENSG00000232629 (Ensembl)
HLA-DRAGeneProductENSG00000204287 (Ensembl)
HLA-DRB1GeneProductENSG00000196126 (Ensembl)
HLA-DRB3GeneProduct3125 (Entrez Gene)
HLA-DRB4GeneProduct3126 (Entrez Gene)
HLA-DRB5GeneProductENSG00000198502 (Ensembl)
HLA-EGeneProductENSG00000204592 (Ensembl)
HLA-FGeneProductENSG00000204642 (Ensembl)
HLA-GGeneProductENSG00000204632 (Ensembl)
ICAM2GeneProductENSG00000108622 (Ensembl)
ICAM3GeneProductENSG00000076662 (Ensembl)
IGF1RGeneProductENSG00000140443 (Ensembl)
IKBKEGeneProductENSG00000263528 (Ensembl)
IL4GeneProductENSG00000113520 (Ensembl)
IQGAP1GeneProductENSG00000140575 (Ensembl)
IRF3GeneProductENSG00000126456 (Ensembl)
IRF7GeneProductENSG00000185507 (Ensembl)
ITGA1GeneProductENSG00000213949 (Ensembl)
ITGA2GeneProductENSG00000164171 (Ensembl)
ITGA3GeneProductENSG00000005884 (Ensembl)
ITGA4GeneProductENSG00000115232 (Ensembl)
ITGA5GeneProductENSG00000161638 (Ensembl)
ITGA6GeneProductENSG00000091409 (Ensembl)
ITGAVGeneProductENSG00000138448 (Ensembl)
ITGB1GeneProductENSG00000150093 (Ensembl)
ITGB3GeneProductENSG00000259207 (Ensembl)
KPNA1GeneProductENSG00000114030 (Ensembl)
LC8GeneProduct8655 (NCBI Protein)
MAPK1GeneProductENSG00000100030 (Ensembl)
MAPK3GeneProductMAPK3 (HGNC)
MBL2GeneProductENSG00000165471 (Ensembl)
MERTKGeneProductENSG00000153208 (Ensembl)
MFGE8GeneProductENSG00000140545 (Ensembl)
MHC1GeneProduct"In humans, the HLAs corresponding to MHC class I are HLA-A, HLA-B, and HLA-C." https://en.wikipedia.org/wiki/MHC_class_I
MHC2GeneProduct"In humans, the MHC class II protein complex is encoded by the human leukocyte antigen gene complex (HLA). HLAs corresponding to MHC class II are HLA-DP, HLA-DM, HLA-DOA, HLA-DOB, HLA-DQ, and HLA-DR." https://en.wikipedia.org/wiki/MHC_class_II
NEDD4GeneProductENSG00000069869 (Ensembl)
NFKB1GeneProductENSG00000109320 (Ensembl)
NFKB2GeneProductENSG00000077150 (Ensembl)
NFKBGeneProductENSG00000109320 (Ensembl)
NPC1GeneProductENSG00000141458 (Ensembl)
NPC2GeneProductENSG00000119655 (Ensembl)
PAK1GeneProductENSG00000149269 (Ensembl)
PIK3CAGeneProductENSG00000121879 (Ensembl)
PIK3CBGeneProductENSG00000051382 (Ensembl)
PIK3CDGeneProductENSG00000171608 (Ensembl)
PIK3R1GeneProductENSG00000145675 (Ensembl)
PIK3R2GeneProductENSG00000105647 (Ensembl)
PIK3R3GeneProductENSG00000117461 (Ensembl)
PIK3RGeneProductENSG00000145675 (Ensembl)
PP1GeneProduct3.1.3.16 (Enzyme Nomenclature)
PRKRAGeneProductENSG00000180228 (Ensembl)
RAB5AGeneProductENSG00000144566 (Ensembl)
RAB7AGeneProductENSG00000075785 (Ensembl)
RAB9AGeneProductENSG00000123595 (Ensembl) PUBMED
RAC1GeneProductENSG00000136238 (Ensembl)
RASA2GeneProductENSG00000155903 (Ensembl)
RELGeneProduct5966 (Entrez Gene)
RELAGeneProductENSG00000173039 (Ensembl)
RELBGeneProductENSG00000104856 (Ensembl)
RHOAGeneProductENSG00000067560 (Ensembl)
RHOBGeneProductENSG00000143878 (Ensembl)
RHOCGeneProductENSG00000155366 (Ensembl)
SCINGeneProductENSG00000006747 (Ensembl)
SOCS3GeneProductENSG00000184557 (Ensembl)
STAT1GeneProductENSG00000115415 (Ensembl)
TBK1GeneProductENSG00000183735 (Ensembl)
TFAP2AGeneProductENSG00000137203 (Ensembl)
TIAM1GeneProductENSG00000156299 (Ensembl)
TIMD4GeneProductENSG00000145850 (Ensembl)
TLR4GeneProductENSG00000136869 (Ensembl)
TOP1GeneProductENSG00000198900 (Ensembl)
TPCN2GeneProductENSG00000162341 (Ensembl)
TSG101GeneProductENSG00000074319 (Ensembl)
TYRO3GeneProductENSG00000092445 (Ensembl)
VAV2GeneProductENSG00000160293 (Ensembl)
VPS11GeneProductENSG00000160695 (Ensembl)
VPS16GeneProductENSG00000215305 (Ensembl)
VPS18GeneProductENSG00000104142 (Ensembl)
VPS33AGeneProductENSG00000139719 (Ensembl)
VPS39GeneProductENSG00000166887 (Ensembl)
VPS41GeneProductENSG00000006715 (Ensembl)
VPS4AGeneProductENSG00000132612 (Ensembl)

Annotated Interactions

No annotated interactions

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