Like all viruses, HIV-1 must co-opt the host cell macromolecular transport and processing machinery. HIV-1 Vpr and Rev proteins play key roles in this co-optation. Efficient HIV-1 replication likewise requires evasion of APOBEC3G-mediated mutagenesis of reverse transcripts, a process mediated by the viral Vif protein.
View original pathway at:Reactome.
Kabachinski G, Schwartz TU.; ''The nuclear pore complex--structure and function at a glance.''; PubMedEurope PMCScholia
Margottin F, Bour SP, Durand H, Selig L, Benichou S, Richard V, Thomas D, Strebel K, Benarous R.; ''A novel human WD protein, h-beta TrCp, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif.''; PubMedEurope PMCScholia
Vodicka MA, Koepp DM, Silver PA, Emerman M.; ''HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage infection.''; PubMedEurope PMCScholia
Saksela K, Cheng G, Baltimore D.; ''Proline-rich (PxxP) motifs in HIV-1 Nef bind to SH3 domains of a subset of Src kinases and are required for the enhanced growth of Nef+ viruses but not for down-regulation of CD4.''; PubMedEurope PMCScholia
Meyer BE, Malim MH.; ''The HIV-1 Rev trans-activator shuttles between the nucleus and the cytoplasm.''; PubMedEurope PMCScholia
Arold S, Franken P, Strub MP, Hoh F, Benichou S, Benarous R, Dumas C.; ''The crystal structure of HIV-1 Nef protein bound to the Fyn kinase SH3 domain suggests a role for this complex in altered T cell receptor signaling.''; PubMedEurope PMCScholia
Askjaer P, Jensen TH, Nilsson J, Englmeier L, Kjems J.; ''The specificity of the CRM1-Rev nuclear export signal interaction is mediated by RanGTP.''; PubMedEurope PMCScholia
Yu X, Yu Y, Liu B, Luo K, Kong W, Mao P, Yu XF.; ''Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex.''; PubMedEurope PMCScholia
Rabut G, Doye V, Ellenberg J.; ''Mapping the dynamic organization of the nuclear pore complex inside single living cells.''; PubMedEurope PMCScholia
Mahboobi SH, Javanpour AA, Mofrad MR.; ''The interaction of RNA helicase DDX3 with HIV-1 Rev-CRM1-RanGTP complex during the HIV replication cycle.''; PubMedEurope PMCScholia
Zapp ML, Green MR.; ''Sequence-specific RNA binding by the HIV-1 Rev protein.''; PubMedEurope PMCScholia
Bischoff FR, Krebber H, Kempf T, Hermes I, Ponstingl H.; ''Human RanGTPase-activating protein RanGAP1 is a homologue of yeast Rna1p involved in mRNA processing and transport.''; PubMedEurope PMCScholia
Roeth JF, Williams M, Kasper MR, Filzen TM, Collins KL.; ''HIV-1 Nef disrupts MHC-I trafficking by recruiting AP-1 to the MHC-I cytoplasmic tail.''; PubMedEurope PMCScholia
Cronshaw JM, Krutchinsky AN, Zhang W, Chait BT, Matunis MJ.; ''Proteomic analysis of the mammalian nuclear pore complex.''; PubMedEurope PMCScholia
Moarefi I, LaFevre-Bernt M, Sicheri F, Huse M, Lee CH, Kuriyan J, Miller WT.; ''Activation of the Src-family tyrosine kinase Hck by SH3 domain displacement.''; PubMedEurope PMCScholia
Janardhan A, Swigut T, Hill B, Myers MP, Skowronski J.; ''HIV-1 Nef binds the DOCK2-ELMO1 complex to activate rac and inhibit lymphocyte chemotaxis.''; PubMedEurope PMCScholia
Marin M, Rose KM, Kozak SL, Kabat D.; ''HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation.''; PubMedEurope PMCScholia
Li K, Warner CK, Hodge JA, Minoshima S, Kudoh J, Fukuyama R, Maekawa M, Shimizu Y, Shimizu N, Wallace DC.; ''A human muscle adenine nucleotide translocator gene has four exons, is located on chromosome 4, and is differentially expressed.''; PubMedEurope PMCScholia
Kamata M, Nitahara-Kasahara Y, Miyamoto Y, Yoneda Y, Aida Y.; ''Importin-alpha promotes passage through the nuclear pore complex of human immunodeficiency virus type 1 Vpr.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
Kobayashi M, Takaori-Kondo A, Miyauchi Y, Iwai K, Uchiyama T.; ''Ubiquitination of APOBEC3G by an HIV-1 Vif-Cullin5-Elongin B-Elongin C complex is essential for Vif function.''; PubMedEurope PMCScholia
Popov S, Rexach M, Ratner L, Blobel G, Bukrinsky M.; ''Viral protein R regulates docking of the HIV-1 preintegration complex to the nuclear pore complex.''; PubMedEurope PMCScholia
Garcia JV, Miller AD.; ''Serine phosphorylation-independent downregulation of cell-surface CD4 by nef.''; PubMedEurope PMCScholia
Le Rouzic E, Mousnier A, Rustum C, Stutz F, Hallberg E, Dargemont C, Benichou S.; ''Docking of HIV-1 Vpr to the nuclear envelope is mediated by the interaction with the nucleoporin hCG1.''; PubMedEurope PMCScholia
Renkema GH, Manninen A, Mann DA, Harris M, Saksela K.; ''Identification of the Nef-associated kinase as p21-activated kinase 2.''; PubMedEurope PMCScholia
Wei P, Garber ME, Fang SM, Fischer WH, Jones KA.; ''A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA.''; PubMedEurope PMCScholia
Daugherty MD, Liu B, Frankel AD.; ''Structural basis for cooperative RNA binding and export complex assembly by HIV Rev.''; PubMedEurope PMCScholia
Wei SJ, Williams JG, Dang H, Darden TA, Betz BL, Humble MM, Chang FM, Trempus CS, Johnson K, Cannon RE, Tennant RW.; ''Identification of a specific motif of the DSS1 protein required for proteasome interaction and p53 protein degradation.''; PubMedEurope PMCScholia
Fritz CC, Green MR.; ''HIV Rev uses a conserved cellular protein export pathway for the nucleocytoplasmic transport of viral RNAs.''; PubMedEurope PMCScholia
Renkema GH, Manninen A, Saksela K.; ''Human immunodeficiency virus type 1 Nef selectively associates with a catalytically active subpopulation of p21-activated kinase 2 (PAK2) independently of PAK2 binding to Nck or beta-PIX.''; PubMedEurope PMCScholia
Jacotot E, Ravagnan L, Loeffler M, Ferri KF, Vieira HL, Zamzami N, Costantini P, Druillennec S, Hoebeke J, Briand JP, Irinopoulou T, Daugas E, Susin SA, Cointe D, Xie ZH, Reed JC, Roques BP, Kroemer G.; ''The HIV-1 viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
Yang X, Gold MO, Tang DN, Lewis DE, Aguilar-Cordova E, Rice AP, Herrmann CH.; ''TAK, an HIV Tat-associated kinase, is a member of the cyclin-dependent family of protein kinases and is induced by activation of peripheral blood lymphocytes and differentiation of promonocytic cell lines.''; PubMedEurope PMCScholia
Grzesiek S, Bax A, Clore GM, Gronenborn AM, Hu JS, Kaufman J, Palmer I, Stahl SJ, Wingfield PT.; ''The solution structure of HIV-1 Nef reveals an unexpected fold and permits delineation of the binding surface for the SH3 domain of Hck tyrosine protein kinase.''; PubMedEurope PMCScholia
Wang JK, Kiyokawa E, Verdin E, Trono D.; ''The Nef protein of HIV-1 associates with rafts and primes T cells for activation.''; PubMedEurope PMCScholia
Raney A, Kuo LS, Baugh LL, Foster JL, Garcia JV.; ''Reconstitution and molecular analysis of an active human immunodeficiency virus type 1 Nef/p21-activated kinase 2 complex.''; PubMedEurope PMCScholia
Sheehy AM, Gaddis NC, Malim MH.; ''The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif.''; PubMedEurope PMCScholia
Henderson BR, Percipalle P.; ''Interactions between HIV Rev and nuclear import and export factors: the Rev nuclear localisation signal mediates specific binding to human importin-beta.''; PubMedEurope PMCScholia
Wei BL, Arora VK, Raney A, Kuo LS, Xiao GH, O'Neill E, Testa JR, Foster JL, Garcia JV.; ''Activation of p21-activated kinase 2 by human immunodeficiency virus type 1 Nef induces merlin phosphorylation.''; PubMedEurope PMCScholia
Voges D, Zwickl P, Baumeister W.; ''The 26S proteasome: a molecular machine designed for controlled proteolysis.''; PubMedEurope PMCScholia
Bischoff FR, Ponstingl H.; ''Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCC1.''; PubMedEurope PMCScholia
Szebeni A, Mehrotra B, Baumann A, Adam SA, Wingfield PT, Olson MO.; ''Nucleolar protein B23 stimulates nuclear import of the HIV-1 Rev protein and NLS-conjugated albumin.''; PubMedEurope PMCScholia
Herrmann CH, Rice AP.; ''Lentivirus Tat proteins specifically associate with a cellular protein kinase, TAK, that hyperphosphorylates the carboxyl-terminal domain of the large subunit of RNA polymerase II: candidate for a Tat cofactor.''; PubMedEurope PMCScholia
Malim MH, Tiley LS, McCarn DF, Rusche JR, Hauber J, Cullen BR.; ''HIV-1 structural gene expression requires binding of the Rev trans-activator to its RNA target sequence.''; PubMedEurope PMCScholia
Yi R, Bogerd HP, Cullen BR.; ''Recruitment of the Crm1 nuclear export factor is sufficient to induce cytoplasmic expression of incompletely spliced human immunodeficiency virus mRNAs.''; PubMedEurope PMCScholia
Fankhauser C, Izaurralde E, Adachi Y, Wingfield P, Laemmli UK.; ''Specific complex of human immunodeficiency virus type 1 rev and nucleolar B23 proteins: dissociation by the Rev response element.''; PubMedEurope PMCScholia
Malim MH, Cullen BR.; ''HIV-1 structural gene expression requires the binding of multiple Rev monomers to the viral RRE: implications for HIV-1 latency.''; PubMedEurope PMCScholia
Swigut T, Shohdy N, Skowronski J.; ''Mechanism for down-regulation of CD28 by Nef.''; PubMedEurope PMCScholia
Yu Q, König R, Pillai S, Chiles K, Kearney M, Palmer S, Richman D, Coffin JM, Landau NR.; ''Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome.''; PubMedEurope PMCScholia
Stove V, Van de Walle I, Naessens E, Coene E, Stove C, Plum J, Verhasselt B.; ''Human immunodeficiency virus Nef induces rapid internalization of the T-cell coreceptor CD8alphabeta.''; PubMedEurope PMCScholia
Suntharalingam M, Wente SR.; ''Peering through the pore: nuclear pore complex structure, assembly, and function.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
Cheng H, Hoxie JP, Parks WP.; ''The conserved core of human immunodeficiency virus type 1 Nef is essential for association with Lck and for enhanced viral replication in T-lymphocytes.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
Zennou V, Perez-Caballero D, Göttlinger H, Bieniasz PD.; ''APOBEC3G incorporation into human immunodeficiency virus type 1 particles.''; PubMedEurope PMCScholia
Agopian K, Wei BL, Garcia JV, Gabuzda D.; ''CD4 and MHC-I downregulation are conserved in primary HIV-1 Nef alleles from brain and lymphoid tissues, but Pak2 activation is highly variable.''; PubMedEurope PMCScholia
Nuclear export of the unspliced and partially spliced HIV-1 transcripts requires the association of the HIV-1 Rev protein with a cis-acting RNA sequence known as the Rev Response Element (RRE) located within the env gene. The RRE forms a stem loop structure that associates with an arginine-rich RNA binding motif (ARM) within Rev.
Crm1 is a nucleocytoplasmic transport factor that is believed to interact with nucleoporins facilitating docking of the RRE-Rev-CRM1-RanGTP complex to the nuclear pore and the translocation of the complex across the nuclear pore complex (see Cullen 1998) Crm1 has been found in complex with two such nucleoporins, CAN/Nup214 and Nup88 which have been shown to be components of the human nuclear pore complex (Fornerod et al., 1997).
Tat associates with the Cyclin T1 subunit of P-TEFb (Cyclin T1:Cdk9) through a region of cysteine-rich and core sequences referred to as the ARM domain within Tat (Wei et al., 1998; see also Herrmann 1995). This interaction is believed to involve metal ions stabilized by cysteine residues in both proteins (Bieniasz et al., 1998; Garber et al., 1998).
Tat associates with the Cyclin T1 subunit of the cellular kinase complex TAK/P-TEFb and recruits this complex to the TAR sequence in the HIV-1 RNA (Wei et al. 1998). This association between TAT, TAR and TAK/P-TEFb is believed to bring the catalytic subunit of TAK/P-TEFb in close proximity to Pol II where it hyperphosphorylates the CTD of Pol II .
Down-regulation of CD28 receptors involves a dileucine-based motif in the second disordered loop of Nef, which connects Nef to adaptor protein (AP) complex, which is a part of cellular endocytosis machinery.
The interaction between Vif and the E3 ubiquitin ligase complex (Cullin5, Elongin B and Elongin C, and Rbx1) takes place through direct binding of the SOCS box motif in the viral protein Vif to the host protein Elongin C. Moreover, a conserved HCCH motif in Vif allows binding to Cullin 5.
The HIV-1 Vif protein associates with the DNA editing enzyme APOBEC3G Marin et al) . The binding site has not yet been mapped but emerging evidence suggest that the N-terminal lregion of Vif is essential for APOBEC3G recognition (Tian et al) . Substitution of a single amino acid in the human APOBEC3G (Asp128Lys) abolishes binding and renders it resistant to HIV-1 Vif (Schrofelbauer et al; Bogerd et al.).
Vpr interacts with importin-alpha through alphaH1 and alphaH2. The interaction via alphaH1 is indispensable for the nuclear entry of Vpr (Kamata et al., 2005) .
APOBEC3G is incorporated into virus particles through its association with components of the viral RNA packaging machinery. It binds to the nucleocapsid portion of Gag (NC), a region of the polyprotein that associates with genomic RNA and functions in RNA encapsidation.
During reverse transcription, APOBEC3G-mediated minus-strand deamination occurs within a CC dinucleotide context over the entire length of the HIV-1 genome (Yu et al., 2004). The polypurine tract is essential for plus strand synthesis and is located at the 3' end of the retroviral genome. HIV-1 encodes an additional central polypurine tract located in the middle of the genome which also serves as primer for plus strand synthesis. Deamination of the minus strand continues throughout its synthesis with the frequency of deamination events increasing from the 5' to 3' regions. A 400bp region downstream of the central polypurine tract seems to be protected from deamination (Wurtzer et al., 2006)
In the target cell, HIV-1-associated APOBEC3G binds to the HIV-1 reverse transcript minus strand and catalyzes the deamination of cytidines in a specific dinucleotide context (e.g., dCC). In contrast, APOBEC3F and APOBEC3B display a preference for dTC.
B23 may function as a shuttle for the import of HIV Rev from the cytoplasm into the nucleus or nucleolus permitting additional rounds of export of viral RNAs.
CRM1 associates directly with Rev through the Rev nuclear export signal (NES) domain and acts as the nuclear export receptor for the Rev-RRE ribonucleoprotein complex.
Vpr interacts with the PTPC component ANT1. This interaction induces mitochondrial membrane permeabilization and release of cytochrome c and apoptotic factors.
The presence of Nef accelerates endocytosis and lysosomal degradation of the transmembrane glycoprotein CD8. Nef facilitates a cascade of protein interactions that ultimately result in the degradation of internalized CD8 protein. The final set of protein interactions that direct Nef to the beta-subunit of the COPI coatomers are at this time unclear. A number of sites within Nef are proposed to be required for CD8 down-regulation, the myristoylation signal and N-terminal anchor regions, the C-terminal flexible loop, and amino acid positions 57 to 58. Consistent with all reported Nef functions, the myristoylation signal was found to be essential for CD8 down-modulation. The flexible loop contains a dileucine-based internalization motif, which is flanked by acidic clusters and is involved in enhanced internalization of the Nef-CD4 complex.
Nef disrupts the transport of major histocompatibility complex class I molecules by first binding to the the cytoplasmic side of the transmembrane complex.
Once the complex of Nef, major histocompatibility complex class I molecules, PACS-1 and AP-1 arrives at the endosome, the MHC I complex is targeted for degradation.
The complex of Nef, major histocompatibility complex class I molecules, PACS-1 and AP-1 is transported from the trans-Golgi network to an endosome, where the MHC I complex will be degraded.
The protein Hck is a member of the Src family of non-receptor tyrosine kinases which is preferentially expressed in haematopoietic cells of the myeloid and B-lymphoid lineages. Src kinases are inhibited by tyrosine-phosphorylation at a carboxy-terminal site. The SH2 domains of these enzymes play an essential role in this regulation by binding to the tyrosine-phosphorylated tail. The SH2 domain of Hck regulates enzymatic activity indirectly; intramolecular interactions between the SH3 and catalytic domains appear to stabilize an inactive form of the kinase. The HIV-1 Nef protein, which is a high-affinity ligand for the Hck SH3 domain, binds to either the downregulated or activated form of Hck causing a large increase in Hck catalytic activity. The intact SH3-binding motif in Nef is crucial for Hck activation.
The HIV Nef protein downregulates CD4 through sequential connection with clathrin-coated pits and the COP1 coatomer, resulting in accelerated endocytosis and lysosomal targeting. The small GTPase ARF1 controls the Nef-induced, COP-mediated late-endosomal targeting of CD4. Nef binds ARF1 directly and can recruit the GTPase onto endosomal membranes, leading to the eventual degradation of CD4 (Faure et al. 2004).
Nef has been shown to bind specifically to a subset of the Src family of kinases. Nef/Fyn interaction centers on a proline-rich motif (Pro-x-x-Pro), which is implicated in SH3 binding. This domain is partially disordered in the absence of the binding partner; when bound this motif fully adopts a left-handed polyproline type II helix conformation upon complex formation with the Fyn SH3 domain. Within this structure the arginine residue (Arg77) of Nef interacts with Asp 100 of the RT loop within the Fyn SH3 domain, and triggers a hydrogen-bond rearrangement which allows the loop to adapt to complement the Nef surface. The Arg96 residue of the Fyn SH3 domain is specifically accommodated in the same hydrophobic pocket of Nef. The Nef-Fyn complex forms in vivo and may have a crucial role in the T cell perturbating action of Nef by altering T cell receptor signaling.
The infectious cycle of primate lentiviruses is intimately linked to interactions between cells of the immune system. Nef, a potent virulence factor, alters cellular environments to increase lentiviral replication in the host, functioning as an adaptor protein. Nef activates Rac in T cell lines and in primary T cells following infection with HIV-1 in the absence of antigenic stimuli. Nef activates Rac by binding the DOCK2-ELMO1 complex, and this interaction is linked to the abilities of Nef to inhibit chemotaxis and promote T cell activation. Nef targets a critical switch that regulates Rac GTPases downstream of chemokine- and antigen-initiated signaling pathways. This interaction enables Nef to influence multiple aspects of T cell function and thus provides an important mechanism by which Nef impacts pathogenesis by primate lentiviruses.
The Nef protein of the primate lentiviruses, including human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV), is a myristylated protein associated with increased viral replication and enhanced pathogenicity. Both the potentiation of T-lymphocyte activation and the enhanced serine-phosphorylation of HIV-1 capsid by Nef correlate with increased viral replication. The Nef proteins from HIV-1 and SIV bind to Lck. The SH3 and SH2 domains of Lck are sufficient for coprecipitation with non-tyrosine-phosphorylated Nef proteins. The conserved core region of HIV-1 Nef is essential for the interaction with Lck and is also important for enhanced HIV-1 replication in T-lymphocytes. The SIV and HIV-1 Nef proteins are differentially tyrosine-phosphorylated. The kinase-active Lck tyrosine-phosphorylates SIVmac239 Nef but does not phosphorylate HIV-1 Nef.
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DataNodes
deaminated minus sssDNA:tRNA
primer:RNA templateminus sssDNA:tRNA
primer:RNA templateComplex:v-ATPase
ComplexComplex:v-ATPase
Complex3' ends of viral
DNA in PICzeta:Lipid Raft:
Pak 2 Complexcomplex:AP-1:PACS-1
Complexcomplex:Ap-1:PACS-1
ComplexsssDNA:tRNA
primer:RNA templatemultimer-bound HIV-1
mRNA:Crm1:Ran:GTP:NPCHIV-1
mRNA:Crm1:Ran:GTPHIV-1
mRNA:Crm1:Ran:GTPHIV-1 mRNA:CRM1
complexProtein
(UniProt:P04601)Annotated Interactions
deaminated minus sssDNA:tRNA
primer:RNA templateminus sssDNA:tRNA
primer:RNA templateminus sssDNA:tRNA
primer:RNA templateComplex:v-ATPase
ComplexComplex:v-ATPase
ComplexComplex:v-ATPase
ComplexComplex:v-ATPase
Complex3' ends of viral
DNA in PIC3' ends of viral
DNA in PIC3' ends of viral
DNA in PICzeta:Lipid Raft:
Pak 2 Complexcomplex:AP-1:PACS-1
Complexcomplex:AP-1:PACS-1
Complexcomplex:Ap-1:PACS-1
Complexcomplex:Ap-1:PACS-1
ComplexSubstitution of a single amino acid in the human APOBEC3G (Asp128Lys) abolishes binding and renders it resistant to HIV-1 Vif (Schrofelbauer et al; Bogerd et al.).
The polypurine tract is essential for plus strand synthesis and is located at the 3' end of the retroviral genome. HIV-1 encodes an additional central polypurine tract located in the middle of the genome which also serves as primer for plus strand synthesis.
Deamination of the minus strand continues throughout its synthesis with the frequency of deamination events increasing from the 5' to 3' regions. A 400bp region downstream of the central polypurine tract seems to be protected from deamination (Wurtzer et al., 2006)
A number of sites within Nef are proposed to be required for CD8 down-regulation, the myristoylation signal and N-terminal anchor regions, the C-terminal flexible loop, and amino acid positions 57 to 58. Consistent with all reported Nef functions, the myristoylation signal was found to be essential for CD8 down-modulation. The flexible loop contains a dileucine-based internalization motif, which is flanked by acidic clusters and is involved in enhanced internalization of the Nef-CD4 complex.
sssDNA:tRNA
primer:RNA templatemultimer-bound HIV-1
mRNA:Crm1:Ran:GTP:NPCmultimer-bound HIV-1
mRNA:Crm1:Ran:GTP:NPCHIV-1
mRNA:Crm1:Ran:GTPHIV-1
mRNA:Crm1:Ran:GTPHIV-1
mRNA:Crm1:Ran:GTPHIV-1
mRNA:Crm1:Ran:GTPHIV-1
mRNA:Crm1:Ran:GTPHIV-1 mRNA:CRM1
complexHIV-1 mRNA:CRM1
complexProtein
(UniProt:P04601)Protein
(UniProt:P04601)Protein
(UniProt:P04601)Protein
(UniProt:P04601)Protein
(UniProt:P04601)Protein
(UniProt:P04601)Protein
(UniProt:P04601)Protein
(UniProt:P04601)Protein
(UniProt:P04601)Protein
(UniProt:P04601)Protein
(UniProt:P04601)Protein
(UniProt:P04601)