vif gene products


Summary: Retrovirally encoded accessary proteins that play an essential role VIRUS REPLICATION. They are found in the cytoplasm of host cells and associate with a variety of host cell proteins. Vif stands for "virion infectivity factor".

Top Publications

  1. Derse D, Hill S, Princler G, Lloyd P, Heidecker G. Resistance of human T cell leukemia virus type 1 to APOBEC3G restriction is mediated by elements in nucleocapsid. Proc Natl Acad Sci U S A. 2007;104:2915-20 pubmed
    ..Elements within the C-terminal extension of the NC domain are highly conserved among the primate T cell leukemia viruses, but this extension is absent in all other retroviral NC proteins...
  2. Garrett E, Tiley L, Cullen B. Rev activates expression of the human immunodeficiency virus type 1 vif and vpr gene products. J Virol. 1991;65:1653-7 pubmed
    ..This activation is shown to result from the reduced utilization of splice sites adjacent to or within the vif and vpr coding sequences. Vif and Vpr therefore belong to the class of late HIV-1 gene products. ..
  3. Mehle A, Goncalves J, Santa Marta M, McPike M, Gabuzda D. Phosphorylation of a novel SOCS-box regulates assembly of the HIV-1 Vif-Cul5 complex that promotes APOBEC3G degradation. Genes Dev. 2004;18:2861-6 pubmed
  4. Mariani R, Chen D, Schröfelbauer B, Navarro F, König R, Bollman B, et al. Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif. Cell. 2003;114:21-31 pubmed
    ..Together these findings suggest that therapeutic intervention that either induced APOBEC3G or blocked its interaction with Vif could be clinically beneficial. ..
  5. Fan L, Peden K. Cell-free transmission of Vif mutants of HIV-1. Virology. 1992;190:19-29 pubmed
    ..No defects in the processing of the virion proteins or the release of particles in the Vif mutants were detected. ..
  6. Dang Y, Wang X, Esselman W, Zheng Y. Identification of APOBEC3DE as another antiretroviral factor from the human APOBEC family. J Virol. 2006;80:10522-33 pubmed
    ..From these studies, we concluded that APOBEC3DE is a new contributor to the intracellular defense network, resulting in suppression of retroviral invasion. ..
  7. Wichroski M, Robb G, Rana T. Human retroviral host restriction factors APOBEC3G and APOBEC3F localize to mRNA processing bodies. PLoS Pathog. 2006;2:e41 pubmed
    ..Taken together, the results of this study reveal a novel link between innate immunity against retroviruses and P-bodies suggesting that APOBEC3G and APOBEC3F could function in the context of P-bodies to restrict HIV-1 replication. ..
  8. Doehle B, Schäfer A, Cullen B. Human APOBEC3B is a potent inhibitor of HIV-1 infectivity and is resistant to HIV-1 Vif. Virology. 2005;339:281-8 pubmed
    ..These studies therefore raise the possibility that activation of the endogenous APOBEC3B gene in primary human lymphoid cells could form a novel and effective strategy for inhibition of HIV-1 replication in vivo. ..
  9. Cancio R, Spadari S, Maga G. Vif is an auxiliary factor of the HIV-1 reverse transcriptase and facilitates abasic site bypass. Biochem J. 2004;383:475-82 pubmed
    ..In addition, Vif was found to promote the bypass of an abasic site by HIV-1 RT. ..

More Information


  1. Dussart S, Courcoul M, Bessou G, Douaisi M, Duverger Y, Vigne R, et al. The Vif protein of human immunodeficiency virus type 1 is posttranslationally modified by ubiquitin. Biochem Biophys Res Commun. 2004;315:66-72 pubmed
    ..Vif is mainly mono-ubiquitinated, a modification known to address the Gag precursor to the virus budding site. ..
  2. Marin M, Rose K, Kozak S, Kabat D. HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation. Nat Med. 2003;9:1398-403 pubmed
    ..These results provide promising approaches for drug discovery. ..
  3. Lecossier D, Bouchonnet F, Clavel F, Hance A. Hypermutation of HIV-1 DNA in the absence of the Vif protein. Science. 2003;300:1112 pubmed
  4. Gabuzda D, Lawrence K, Langhoff E, Terwilliger E, Dorfman T, Haseltine W, et al. Role of vif in replication of human immunodeficiency virus type 1 in CD4+ T lymphocytes. J Virol. 1992;66:6489-95 pubmed
    ..Spehner, M.-P. Kieny, and J.-P. Lecocq, J. Virol. 65:1325-1331, 1991). These studies demonstrate that vif enhances viral infectivity during virus production and also suggest that vif is likely to be important for natural infections. ..
  5. Yang X, Goncalves J, Gabuzda D. Phosphorylation of Vif and its role in HIV-1 replication. J Biol Chem. 1996;271:10121-9 pubmed
    ..These studies suggest that phosphorylation of Vif by a serine/threonine protein kinase(s) plays an important role in regulating HIV-1 replication and infectivity. ..
  6. Zhang H, Pomerantz R, Dornadula G, Sun Y. Human immunodeficiency virus type 1 Vif protein is an integral component of an mRNP complex of viral RNA and could be involved in the viral RNA folding and packaging process. J Virol. 2000;74:8252-61 pubmed
    ..Further studies regarding Vif-RNA interaction in virus-producing cells will be important for studying the function of Vif in the HIV-1 life cycle. ..
  7. Liu H, Wu X, Newman M, Shaw G, Hahn B, Kappes J. The Vif protein of human and simian immunodeficiency viruses is packaged into virions and associates with viral core structures. J Virol. 1995;69:7630-8 pubmed
    ..These results indicate that Vif represents an integral component of HIV and SIV particles and raise the possibility that it plays a direct role in early replication events. ..
  8. Harris R, Bishop K, Sheehy A, Craig H, Petersen Mahrt S, Watt I, et al. DNA deamination mediates innate immunity to retroviral infection. Cell. 2003;113:803-9 pubmed
    ..These findings imply that targeted DNA deamination is a major strategy of innate immunity to retroviruses and likely also contributes to the sequence variation observed in many viruses (including HIV)...
  9. Alce T, Popik W. APOBEC3G is incorporated into virus-like particles by a direct interaction with HIV-1 Gag nucleocapsid protein. J Biol Chem. 2004;279:34083-6 pubmed
    ..Binding to the NC domain would ensure that APOBEC3G will be concentrated in the viral core of mature HIV-1, in close proximity to the reverse transcription complex...
  10. Navarro F, Bollman B, Chen H, König R, Yu Q, Chiles K, et al. Complementary function of the two catalytic domains of APOBEC3G. Virology. 2005;333:374-86 pubmed
    ..These findings suggest a model in which CD1 mediates encapsidation and RNA binding while CD2 mediates cytidine deaminase activity. Interestingly, HTLV-I was relatively resistant to the antiviral effects of encapsidated APOBEC3G. ..
  11. Sasada A, Takaori Kondo A, Shirakawa K, Kobayashi M, Abudu A, Hishizawa M, et al. APOBEC3G targets human T-cell leukemia virus type 1. Retrovirology. 2005;2:32 pubmed
    ..These results suggest that APOBEC3G might act on HTLV-1 through different mechanisms from that on HIV-1 and contribute to the unique features of HTLV-1 infection and transmission. ..
  12. Schröfelbauer B, Chen D, Landau N. A single amino acid of APOBEC3G controls its species-specific interaction with virion infectivity factor (Vif). Proc Natl Acad Sci U S A. 2004;101:3927-32 pubmed
    ..Based on the crystal structure of the distantly related Escherichia coli cytidine deaminase, we propose that this amino acid is positioned on a solvent-exposed loop of APOBEC3G on the same face of the protein as the catalytic site. ..
  13. Akari H, Fujita M, Kao S, Khan M, Shehu Xhilaga M, Adachi A, et al. High level expression of human immunodeficiency virus type-1 Vif inhibits viral infectivity by modulating proteolytic processing of the Gag precursor at the p2/nucleocapsid processing site. J Biol Chem. 2004;279:12355-62 pubmed
    ..However, the accumulation of such processing intermediates at high levels of Vif is inhibitory. Thus, rapid intracellular degradation of Vif may have evolved as a mechanism to prevent such inhibitory effects of Vif. ..
  14. Cullen B. Role and mechanism of action of the APOBEC3 family of antiretroviral resistance factors. J Virol. 2006;80:1067-76 pubmed
  15. Gaddis N, Chertova E, Sheehy A, Henderson L, Malim M. Comprehensive investigation of the molecular defect in vif-deficient human immunodeficiency virus type 1 virions. J Virol. 2003;77:5810-20 pubmed
    ..Based on the inability of this comprehensive analysis to uncover molecular defects in Delta vif virions, we speculate that such defects are likely to be subtle and/or rare. ..
  16. Stopak K, de Noronha C, Yonemoto W, Greene W. HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracellular stability. Mol Cell. 2003;12:591-601 pubmed
  17. Gu Y, Sundquist W. Good to CU. Nature. 2003;424:21-2 pubmed
  18. Zhang H, Yang B, Pomerantz R, Zhang C, Arunachalam S, Gao L. The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA. Nature. 2003;424:94-8 pubmed
    ..Importantly, the accumulation of CEM15-mediated non-lethal hypermutation in the replicating viral genome could potently contribute to the genetic variation of primate lentiviral populations. ..
  19. Karczewski M, Strebel K. Cytoskeleton association and virion incorporation of the human immunodeficiency virus type 1 Vif protein. J Virol. 1996;70:494-507 pubmed
    ..We propose a model in which Vif has a crucial function as a virion component either by regulating virus maturation or following virus entry into a host cell possibly involving an interaction with the cellular cytoskeletal network. ..
  20. Henriet S, Richer D, Bernacchi S, Decroly E, Vigne R, Ehresmann B, et al. Cooperative and specific binding of Vif to the 5' region of HIV-1 genomic RNA. J Mol Biol. 2005;354:55-72 pubmed
    ..Interestingly, our results suggest also that Vif could bind the viral RNA in order to protect it from the action of the antiviral factor APOBEC-3G/3F. ..
  21. Rose K, Marin M, Kozak S, Kabat D. Regulated production and anti-HIV type 1 activities of cytidine deaminases APOBEC3B, 3F, and 3G. AIDS Res Hum Retroviruses. 2005;21:611-9 pubmed
    ..Although A3G and/or A3F inactivate HIV-1(Deltavif) and are neutralized by Vif, the antiviral properties of cell lines are also influenced by other cellular and viral factors. ..
  22. Han Y, Wang X, Dang Y, Zheng Y. Demonstration of a novel HIV-1 restriction phenotype from a human T cell line. PLoS ONE. 2008;3:e2796 pubmed publisher
    ..These results clearly indicate that CEM.NKR cells express a HIV inhibitory gene(s). Further characterization of this novel gene product(s) will reveal a new antiretroviral mechanism that directly inactivates wild type HIV-1. ..
  23. Kozak S, Marin M, Rose K, Bystrom C, Kabat D. The anti-HIV-1 editing enzyme APOBEC3G binds HIV-1 RNA and messenger RNAs that shuttle between polysomes and stress granules. J Biol Chem. 2006;281:29105-19 pubmed
    ..Many proteins and RNAs associated with A3G are excluded from A3G-containing virions, implying that A3G competitively partitions into virions based on affinity for HIV-1 RNA. ..
  24. Jónsson S, Haché G, Stenglein M, Fahrenkrug S, Andresdottir V, Harris R. Evolutionarily conserved and non-conserved retrovirus restriction activities of artiodactyl APOBEC3F proteins. Nucleic Acids Res. 2006;34:5683-94 pubmed
    ..Together, these studies indicate that some properties of the mammal-specific, APOBEC3-dependent retroelement restriction system are necessary and conserved, but others are simultaneously modular and highly adaptable...
  25. Yu Q, Chen D, König R, Mariani R, Unutmaz D, Landau N. APOBEC3B and APOBEC3C are potent inhibitors of simian immunodeficiency virus replication. J Biol Chem. 2004;279:53379-86 pubmed
    ..APOBEC3F was found to be active against SIV and sensitive to SIV(mac) Vif. These findings raise the possibility that the different APOBEC3 family members function to neutralize specific lentiviruses. ..
  26. Kao S, Akari H, Khan M, Dettenhofer M, Yu X, Strebel K. Human immunodeficiency virus type 1 Vif is efficiently packaged into virions during productive but not chronic infection. J Virol. 2003;77:1131-40 pubmed
    ..The results from our study provide novel insights into the biochemical properties of Vif and offer an explanation for the reported differences regarding Vif packaging. ..
  27. Kao S, Khan M, Miyagi E, Plishka R, Buckler White A, Strebel K. The human immunodeficiency virus type 1 Vif protein reduces intracellular expression and inhibits packaging of APOBEC3G (CEM15), a cellular inhibitor of virus infectivity. J Virol. 2003;77:11398-407 pubmed
  28. Khan M, Aberham C, Kao S, Akari H, Gorelick R, Bour S, et al. Human immunodeficiency virus type 1 Vif protein is packaged into the nucleoprotein complex through an interaction with viral genomic RNA. J Virol. 2001;75:7252-65 pubmed
    ..Our data suggest that the specific association of Vif with the viral nucleoprotein complex might be functionally significant and could be a critical requirement for infectivity of viruses produced from restrictive host cells. ..
  29. Mehle A, Strack B, Ancuta P, Zhang C, McPike M, Gabuzda D. Vif overcomes the innate antiviral activity of APOBEC3G by promoting its degradation in the ubiquitin-proteasome pathway. J Biol Chem. 2004;279:7792-8 pubmed
    ..These results suggest that Vif functions by targeting APOBEC3G for degradation via the ubiquitin-proteasome pathway and implicate the proteasome as a site of dynamic interplay between microbial and cellular defenses. ..
  30. Wiegand H, Doehle B, Bogerd H, Cullen B. A second human antiretroviral factor, APOBEC3F, is suppressed by the HIV-1 and HIV-2 Vif proteins. EMBO J. 2004;23:2451-8 pubmed
    ..In contrast, both genes are quiescent in the permissive CEM derivative CEM-SS. Together, these data argue that HIV-1 Vif has evolved to suppress at least two distinct but related human antiretroviral DNA-editing enzymes. ..
  31. Kao S, Miyagi E, Khan M, Takeuchi H, Opi S, Goila Gaur R, et al. Production of infectious human immunodeficiency virus type 1 does not require depletion of APOBEC3G from virus-producing cells. Retrovirology. 2004;1:27 pubmed
    ..Thus, depletion of APOBEC3G from Vif expressing cells as suggested previously is not a universal property of Vif and thus is not imperative for the production of infectious virions. ..
  32. Schäfer A, Bogerd H, Cullen B. Specific packaging of APOBEC3G into HIV-1 virions is mediated by the nucleocapsid domain of the gag polyprotein precursor. Virology. 2004;328:163-8 pubmed
    ..Surprisingly, RNA was also found to be essential for formation of the nucleocapsid--APOBEC3G complex in vitro, thus raising the possibility that RNA may form a bridge between these two proteins...
  33. Madani N, Kabat D. An endogenous inhibitor of human immunodeficiency virus in human lymphocytes is overcome by the viral Vif protein. J Virol. 1998;72:10251-5 pubmed
    ..This strongly suggests that nonpermissive cells, the natural targets of HIV-1, contain a potent endogenous inhibitor of HIV-1 replication that is overcome by Vif. ..
  34. Goff S. Death by deamination: a novel host restriction system for HIV-1. Cell. 2003;114:281-3 pubmed
    ..The enzyme attacks viral DNA as it is synthesized in infected cells and prevents the formation of functional proviruses. The Vif gene of HIV-1 blocks this host restriction and so allows virus replication. ..
  35. Sheehy A, Gaddis N, Choi J, Malim M. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature. 2002;418:646-50 pubmed
    ..Because the Vif:CEM15 regulatory circuit is critical for HIV-1 replication, perturbing the circuit may be a promising target for future HIV/AIDS therapies. ..
  36. Sheehy A, Gaddis N, Malim M. The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif. Nat Med. 2003;9:1404-7 pubmed
    ..Our findings indicate that pharmacologic strategies aimed at stabilizing APOBEC3G in HIV-1 infected cells should be explored as potential HIV/AIDS therapeutics. ..
  37. Xu H, Svarovskaia E, Barr R, Zhang Y, Khan M, Strebel K, et al. A single amino acid substitution in human APOBEC3G antiretroviral enzyme confers resistance to HIV-1 virion infectivity factor-induced depletion. Proc Natl Acad Sci U S A. 2004;101:5652-7 pubmed
    ..The HIV-1 Vif-resistant mutant APOBEC3G could provide a gene therapy approach to combat HIV-1 infection. ..
  38. Cen S, Guo F, Niu M, Saadatmand J, Deflassieux J, Kleiman L. The interaction between HIV-1 Gag and APOBEC3G. J Biol Chem. 2004;279:33177-84 pubmed
  39. Simon J, Fouchier R, Southerling T, Guerra C, Grant C, Malim M. The Vif and Gag proteins of human immunodeficiency virus type 1 colocalize in infected human T cells. J Virol. 1997;71:5259-67 pubmed
    ..As a result, Vif is able to exert its modulatory effect(s) on these late steps of the virus life cycle. ..
  40. Zheng Y, Irwin D, Kurosu T, Tokunaga K, Sata T, Peterlin B. Human APOBEC3F is another host factor that blocks human immunodeficiency virus type 1 replication. J Virol. 2004;78:6073-6 pubmed
    ..Thus, APOBEC family members might have evolved as a general defense mechanism of the body against retroviruses, retrotransposons, and other mobile genetic elements. ..
  41. Nascimbeni M, Bouyac M, Rey F, Spire B, Clavel F. The replicative impairment of Vif- mutants of human immunodeficiency virus type 1 correlates with an overall defect in viral DNA synthesis. J Gen Virol. 1998;79 ( Pt 8):1945-50 pubmed
    ..We conclude that the primary replicative defect of Vif- virus involves the capacity of the reverse transcription complex of HIV-1 to efficiently elongate viral DNA, resulting in an inability to produce full-length viral DNA genomes. ..
  42. Sawyer S, Emerman M, Malik H. Ancient adaptive evolution of the primate antiviral DNA-editing enzyme APOBEC3G. PLoS Biol. 2004;2:E275 pubmed
    ..Despite being only recently discovered, editing of RNA and DNA may thus represent an ancient form of host defense in primate genomes. ..
  43. Pace C, Keller J, Nolan D, James I, Gaudieri S, Moore C, et al. Population level analysis of human immunodeficiency virus type 1 hypermutation and its relationship with APOBEC3G and vif genetic variation. J Virol. 2006;80:9259-69 pubmed
    ..These data indicate that APOBEC3G-induced HIV-1 hypermutation represents a potent host antiviral factor in vivo and that the APOBEC3G-vif interaction may represent a valuable therapeutic target. ..
  44. Newman E, Holmes R, Craig H, Klein K, Lingappa J, Malim M, et al. Antiviral function of APOBEC3G can be dissociated from cytidine deaminase activity. Curr Biol. 2005;15:166-70 pubmed
    ..Accordingly, we propose that APOBEC3G can achieve an anti-HIV-1 effect through an undescribed mechanism that is distinct from cytidine deamination. ..
  45. Mangeat B, Turelli P, Liao S, Trono D. A single amino acid determinant governs the species-specific sensitivity of APOBEC3G to Vif action. J Biol Chem. 2004;279:14481-3 pubmed
    ..Furthermore, we show that this phenotype correlates with the ability of Vif to bind APOBEC3G and interfere with its incorporation into virions. These results shed light on an important determinant of the tropism of primate lentiviruses. ..
  46. Santa Marta M, da Silva F, Fonseca A, Goncalves J. HIV-1 Vif can directly inhibit apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G-mediated cytidine deamination by using a single amino acid interaction and without protein degradation. J Biol Chem. 2005;280:8765-75 pubmed
    ..In conclusion, our experiments suggest a complement to the model of Vif-induced degradation of APOBEC3G by bringing to relevance that deaminase inhibition can also result from a direct interaction with Vif protein. ..
  47. Wichroski M, Ichiyama K, Rana T. Analysis of HIV-1 viral infectivity factor-mediated proteasome-dependent depletion of APOBEC3G: correlating function and subcellular localization. J Biol Chem. 2005;280:8387-96 pubmed
    ..Taken together, these results demonstrate that cytoplasmic Vif-APOBEC3G interactions are required but are not sufficient for Vif to modulate APOBEC3G and can be monitored by co-localization in vivo. ..
  48. Harris R, Liddament M. Retroviral restriction by APOBEC proteins. Nat Rev Immunol. 2004;4:868-77 pubmed
    ..This APOBEC abundance might help to tip the balance in favour of cellular defences. ..
  49. Liu B, Yu X, Luo K, Yu Y, Yu X. Influence of primate lentiviral Vif and proteasome inhibitors on human immunodeficiency virus type 1 virion packaging of APOBEC3G. J Virol. 2004;78:2072-81 pubmed
    ..These results suggest that Vif function is required during virus assembly to remove APOBEC3G from packaging into released virions. Once packaged, virion-associated Vif could not efficiently block the antiviral activity of APOBEC3G. ..
  50. Bardy M, Gay B, Pebernard S, Chazal N, Courcoul M, Vigne R, et al. Interaction of human immunodeficiency virus type 1 Vif with Gag and Gag-Pol precursors: co-encapsidation and interference with viral protease-mediated Gag processing. J Gen Virol. 2001;82:2719-33 pubmed
  51. Navarro F, Landau N. Recent insights into HIV-1 Vif. Curr Opin Immunol. 2004;16:477-82 pubmed
    ..The enzyme lies in the virion, waiting to wreak havoc on the viral genome in the next round of virus replication--unless it is first caught by Vif. ..
  52. Aires da Silva F, Santa Marta M, Freitas Vieira A, Mascarenhas P, Barahona I, Moniz Pereira J, et al. Camelized rabbit-derived VH single-domain intrabodies against Vif strongly neutralize HIV-1 infectivity. J Mol Biol. 2004;340:525-42 pubmed
    ..The present study strongly suggests that camelization of rabbit VH domains is a potentially useful approach for engineering intrabodies for gene therapy. ..