vpu genes


Summary: DNA sequences that form the coding region for the HIV-1 regulatory protein vpu (viral protein U) that greatly increases the export of virus particles from infected cells. The vpu genes are not present in HIV-2 or SIMIAN IMMUNODEFICIENCY VIRUS.

Top Publications

  1. Bour S, Perrin C, Akari H, Strebel K. The human immunodeficiency virus type 1 Vpu protein inhibits NF-kappa B activation by interfering with beta TrCP-mediated degradation of Ikappa B. J Biol Chem. 2001;276:15920-8 pubmed
    ..However, in the presence of Vpu, this HIV-mediated NF-kappaB activation was markedly reduced. These results suggest that Vpu modulates both virus- and cytokine-induced activation of NF-kappaB in HIV-1-infected cells. ..
  2. Dunn C, Beyer C, Kieny M, Gloeckler L, Schmitt D, Gut J, et al. High viral load and CD4 lymphopenia in rhesus and cynomolgus macaques infected by a chimeric primate lentivirus constructed using the env, rev, tat, and vpu genes from HIV-1 Lai. Virology. 1996;223:351-61 pubmed
    ..We have constructed a chimeric virus in which the env, rev, tat, and vpu genes of HIV-1 Lai replace the env, rev, and tat genes of the SIVmac239 genome...
  3. Yedavalli V, Husain M, Horodner A, Ahmad N. Molecular characterization of HIV type 1 vpu genes from mothers and infants after perinatal transmission. AIDS Res Hum Retroviruses. 2001;17:1089-98 pubmed
    ..12% frequency of intact vpu open reading frames. The heterogeneity of vpu genes between epidemiologically linked mother-infant pairs was lower compared with epidemiologically unlinked ..
  4. Cornelissen M, Kuiken C, Zorgdrager F, Hartman S, Goudsmit J. Gross defects in the vpr and vpu genes of HIV type 1 cannot explain the differences in RNA copy number between long-term asymptomatics and progressors. AIDS Res Hum Retroviruses. 1997;13:247-52 pubmed
    ..to examine whether a difference in viral load can be attributed to infection by viruses having distinct vpr and vpu genes. Sequencing of vpr and vpu genes from serum samples collected at seroconversion from both long-term ..
  5. Saurya S, Lichtenstein Z, Karpas A. Characterization of pol, vif, vpr, and vpu genes of HIV type 1 in AIDS patients with high viral load and stable CD4+ T cell counts on combination therapy. AIDS Res Hum Retroviruses. 2002;18:1151-5 pubmed
    ..In the same patient, the Vif protein was also truncated because of the deletion of 100 nucleotides at the 3' end of the vif gene. ..
  6. Bell C, Connell B, Capovilla A, Venter W, Stevens W, Papathanasopoulos M. Molecular characterization of the HIV type 1 subtype C accessory genes vif, vpr, and vpu. AIDS Res Hum Retroviruses. 2007;23:322-30 pubmed
    ..These results indicate that antiviral drugs that target the conserved functional domains within Vif, Vpr or Vpu could be active against all circulating subtypes, including HIV-1 subtype C. ..
  7. Aulicino P, Holmes E, Rocco C, Mangano A, Sen L. Extremely rapid spread of human immunodeficiency virus type 1 BF recombinants in Argentina. J Virol. 2007;81:427-9 pubmed
    ..72 months. This rapid population growth is compatible with an elevated fitness for subtype BF compared to that for "pure" B and F viruses. ..
  8. Haseltine W. Molecular biology of the human immunodeficiency virus type 1. FASEB J. 1991;5:2349-60 pubmed
    ..However, enough insight has been gained into the structure and function of each of these components to provide a firm basis for rational antiviral drug development. ..
  9. Yao X, Garzon S, Boisvert F, Haseltine W, Cohen E. The effect of vpu on HIV-1-induced syncytia formation. J Acquir Immune Defic Syndr. 1993;6:135-41 pubmed
    ..By reducing the concentration of gp 120 at the cell surface, vpu limits cell killing by syncytia formation. ..

More Information


  1. Levesque K, Finzi A, Binette J, Cohen E. Role of CD4 receptor down-regulation during HIV-1 infection. Curr HIV Res. 2004;2:51-9 pubmed
  2. Sakuragi S, Shibata R, Mukai R, Komatsu T, Fukasawa M, Sakai H, et al. Infection of macaque monkeys with a chimeric human and simian immunodeficiency virus. J Gen Virol. 1992;73 ( Pt 11):2983-7 pubmed
    ..The hybrid nature of the isolated viruses was verified by Southern and Western blotting analyses. Both of the monkeys infected with the chimera elicited a humoral antibody response against the virus. ..
  3. Reimann K, Li J, Voss G, Lekutis C, Tenner Racz K, Racz P, et al. An env gene derived from a primary human immunodeficiency virus type 1 isolate confers high in vivo replicative capacity to a chimeric simian/human immunodeficiency virus in rhesus monkeys. J Virol. 1996;70:3198-206 pubmed
    ..With the demonstration that a chimeric SHIV can replicate to high levels during primary infection in rhesus monkeys, this model can now be used to define genetic determinants of HIV-1 pathogenicity. ..
  4. Ueno T, Sakai H. [The function of accessory genes of HIV-1]. Nihon Rinsho. 2002;60:674-80 pubmed
    ..In this review, we summarize new observations mainly about the interactions between auxiliary genes and host cell functions. ..
  5. Gibbs J, Regier D, Desrosiers R. Construction and in vitro properties of HIV-1 mutants with deletions in "nonessential" genes. AIDS Res Hum Retroviruses. 1994;10:343-50 pubmed
    ..This collection of HIV-1 deletion mutants will be useful for elucidating the functions of these genes and for investigating antiviral immunity in animal models. ..
  6. Taniguchi Y, Takehisa J, Bikandou B, Mboudjeka I, N Doundou N Kodia M, Obengui -, et al. Genetic subtypes of HIV type 1 based on the vpu/env sequences in the Republic of Congo. AIDS Res Hum Retroviruses. 2002;18:79-83 pubmed
    ..These data suggest that the majority of HIV-1 subtypes circulating in the Republic of Congo have mosaic structures and may have been derived from independent recombinational events. ..
  7. Vallejo A, Gurtler L, Zekeng L, Hewlett I. Nucleotide sequence analysis of the accessory genes of HIV-1 group O isolates. Virus Res. 2003;91:189-93 pubmed
    ..Phylogenetic analysis of these sequences suggests that group O viruses could be differentiated into at least four different clusters. ..
  8. Dazza M, Ekwalanga M, Nende M, Shamamba K, Bitshi P, Paraskevis D, et al. Characterization of a novel vpu-harboring simian immunodeficiency virus from a Dent's Mona monkey (Cercopithecus mona denti). J Virol. 2005;79:8560-71 pubmed
    ..Although it harbors a vpu gene, SIVden is phylogenetically closer to SIVdeb isolated from De Brazza's monkeys (Cercopithecus neglectus), which lacks a vpu gene, than to Cercopithecus monkey viruses, which harbor a vpu sequence...
  9. Joag S, Li Z, Wang C, Jia F, Foresman L, Adany I, et al. Chimeric SHIV that causes CD4+ T cell loss and AIDS in rhesus macaques. J Med Primatol. 1998;27:59-64 pubmed
    ..Animals infected by either mucosal or parenteral routes of infection had a similar course of infection. ..
  10. Rapaport E, Casella C, Ikl -, Mustafa F, Isaak D, Finkel T. Mapping of HIV-1 determinants of apoptosis in infected T cells. Virology. 1998;252:407-17 pubmed
    ..We postulate that, in vivo, HIV variants that do not induce rapid apoptosis in the cells they infect may have a selective advantage. ..
  11. Chen M, Lee K, Hung C, Chuang C, Chou M. Strategies for diagnosing HIV-1 infection in atypical Western blots. Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi. 1997;30:135-44 pubmed
    ..We propose to diagnose HIV-1 infection and to differentiate the infection of HIV-1 from HIV-2 in these cases by using nested polymerase chain reaction (PCR) to demonstrate the presence of HIV-1 specific vpu gene. ..
  12. Chen Z, Zhao X, Huang Y, Gettie A, Ba L, Blanchard J, et al. CD4+ lymphocytopenia in acute infection of Asian macaques by a vaginally transmissible subtype-C, CCR5-tropic Simian/Human Immunodeficiency Virus (SHIV). J Acquir Immune Defic Syndr. 2002;30:133-45 pubmed
    ..Our data indicate that the R5-mediated CD4+ lymphocytopenia in the gut is likely independent of HIV-1 genotypes and of the function of vpu at the acute phase of viral infection. ..
  13. Du B, Wolf A, Lee S, Terwilliger E. Changes in the host range and growth potential of an HIV-1 clone are conferred by the vpu gene. Virology. 1993;195:260-4 pubmed
  14. Sakai H, Kawamura M, Sakuragi J, Sakuragi S, Shibata R, Ishimoto A, et al. Integration is essential for efficient gene expression of human immunodeficiency virus type 1. J Virol. 1993;67:1169-74 pubmed
    ..Together with an observation that the mutant lacked the ability to integrate, these results indicated that the integration was required for efficient viral gene expression and productive infection of human immunodeficiency virus type 1...
  15. Courgnaud V, Salemi M, Pourrut X, Mpoudi Ngole E, Abela B, Auzel P, et al. Characterization of a novel simian immunodeficiency virus with a vpu gene from greater spot-nosed monkeys (Cercopithecus nictitans) provides new insights into simian/human immunodeficiency virus phylogeny. J Virol. 2002;76:8298-309 pubmed
    ..The complex genomic structure of SIVgsn, the presence of a vpu gene, and its relatedness to SIVcpz in the envelope suggest a link between SIVgsn and SIVcpz and provide new insights about the origin of SIVcpz in chimpanzees...
  16. Balliet J, Kolson D, Eiger G, Kim F, McGann K, Srinivasan A, et al. Distinct effects in primary macrophages and lymphocytes of the human immunodeficiency virus type 1 accessory genes vpr, vpu, and nef: mutational analysis of a primary HIV-1 isolate. Virology. 1994;200:623-31 pubmed
    ..The essential functions of these accessory genes in HIV-1 infection may be related to their combined effects in facilitating productive infection of macrophages. ..
  17. Gibbs J, Regier D, Desrosiers R. Construction and in vitro properties of SIVmac mutants with deletions in "nonessential" genes. AIDS Res Hum Retroviruses. 1994;10:607-16 pubmed
  18. Anson D, Dunning K. Codon-optimized reading frames facilitate high-level expression of the HIV-1 minor proteins. Mol Biotechnol. 2005;31:85-8 pubmed
    ..Northern blot analysis shows that the increase in expression found with the codon-optimized reading frames is largely owing to increased steady-state mRNA levels. ..
  19. Liegeois F, Courgnaud V, Switzer W, Murphy H, Loul S, Aghokeng A, et al. Molecular characterization of a novel simian immunodeficiency virus lineage (SIVtal) from northern talapoins (Miopithecus ogouensis). Virology. 2006;349:55-65 pubmed
    ..Although northern talapoins belong to the Miopithecus genus, their SIVs belong to the Cercopithecus SIV lineage, suggesting evolution from a common ancestor or cross-species transmission between both primate genera. ..
  20. Chen B, Gandhi R, Baltimore D. CD4 down-modulation during infection of human T cells with human immunodeficiency virus type 1 involves independent activities of vpu, env, and nef. J Virol. 1996;70:6044-53 pubmed
    ..HIV therefore has three genes that are able to independently down-modulate CD4; together, they can eliminate the bulk of cell surface CD4. ..
  21. Reiser J, Harmison G, Kluepfel Stahl S, Brady R, Karlsson S, Schubert M. Transduction of nondividing cells using pseudotyped defective high-titer HIV type 1 particles. Proc Natl Acad Sci U S A. 1996;93:15266-71 pubmed
    ..Human CD34+ cells were transduced efficiently using HIV-1 pseudotype particles without prior stimulation with cytokines. ..
  22. Courgnaud V, Abela B, Pourrut X, Mpoudi Ngole E, Loul S, Delaporte E, et al. Identification of a new simian immunodeficiency virus lineage with a vpu gene present among different cercopithecus monkeys (C. mona, C. cephus, and C. nictitans) from Cameroon. J Virol. 2003;77:12523-34 pubmed
  23. Joag S, Liu Z, Stephens E, Smith M, Kumar A, Li Z, et al. Oral immunization of macaques with attenuated vaccine virus induces protection against vaginally transmitted AIDS. J Virol. 1998;72:9069-78 pubmed
    ..This is the first demonstration of protection against virulent SHIV administered by the intravaginal route. This study supports the concept that sexually transmitted HIV disease can be prevented by parenteral or oral immunization. ..
  24. Ayyavoo V, Nagashunmugam T, Phung M, Buckner C, Kudckodkar S, Le P, et al. Construction of attenuated HIV-1 accessory gene immunization cassettes. Vaccine. 1998;16:1872-9 pubmed
    ..This strategy can be used generally to develop an effective, safe DNA vaccine for any pathogen. ..
  25. Coskun A, van Maanen M, Nguyen V, Sutton R. Human chromosome 2 carries a gene required for production of infectious human immunodeficiency virus type 1. J Virol. 2006;80:3406-15 pubmed
    ..These results suggest that processing of HIV Gag can be corrected by one or more genes present on human chromosome 2 to allow production of infectious HIV from murine cells. ..
  26. Dejucq N. HIV-1 replication in CD4+ T cell lines: the effects of adaptation on co-receptor use, tropism, and accessory gene function. J Leukoc Biol. 2000;68:331-7 pubmed
    ..g., vpu) not required for replication in rapidly dividing cell lines may also occur in vitro, abrogating replication in primary cell types such as macrophages. Such mutations, however, are normally selected against in vivo. ..
  27. Westervelt P, Henkel T, Trowbridge D, Orenstein J, Heuser J, Gendelman H, et al. Dual regulation of silent and productive infection in monocytes by distinct human immunodeficiency virus type 1 determinants. J Virol. 1992;66:3925-31 pubmed
    ..Clones with the env determinant but lacking either functional vpr or vpu genes generated lower replication levels in monocytes...
  28. Nguyen K, Llano M, Akari H, Miyagi E, Poeschla E, Strebel K, et al. Codon optimization of the HIV-1 vpu and vif genes stabilizes their mRNA and allows for highly efficient Rev-independent expression. Virology. 2004;319:163-75 pubmed
  29. Hout D, Mulcahy E, Pacyniak E, Gomez L, Gomez M, Stephens E. Vpu: a multifunctional protein that enhances the pathogenesis of human immunodeficiency virus type 1. Curr HIV Res. 2004;2:255-70 pubmed
    ..This review will focus on the current understanding of the structure-function relationships of Vpu protein and recent advances using the SHIV model to assess the role of Vpu in HIV-1 pathogenesis. ..
  30. D Agostino D, Felber B, Harrison J, Pavlakis G. The Rev protein of human immunodeficiency virus type 1 promotes polysomal association and translation of gag/pol and vpu/env mRNAs. Mol Cell Biol. 1992;12:1375-86 pubmed
    ..These findings indicate that the presence of Rev is required along the entire mRNA transport and utilization pathway for the stabilization, correct localization, and efficient translation of RRE-containing mRNAs. ..
  31. Karn J. Control of human immunodeficiency virus replication by the tat, rev, nef and protease genes. Curr Opin Immunol. 1991;3:526-36 pubmed
  32. Nishino Y, Nakaya T, Fujinaga K, Kishi M, Azuma I, Ikuta K. Persistent infection of MT-4 cells by human immunodeficiency virus type 1 becomes increasingly likely with in vitro serial passage of wild-type but not nef mutant virus. J Gen Virol. 1994;75 ( Pt 9):2241-51 pubmed
    ..Our results also suggest an important role for the nef gene product in the generation of HIV-1 strains that are less cytopathogenic. ..
  33. Sakai H, Tokunaga K, Kawamura M, Adachi A. Function of human immunodeficiency virus type 1 Vpu protein in various cell types. J Gen Virol. 1995;76 ( Pt 11):2717-22 pubmed
    ..Likewise, CD4 gene expression had no effects on Vpu function. In the other cell lines tested, Vpu protein was not important for virion release, and the vpu mutant clone generated a normal level of progeny virions upon transfection. ..
  34. Thomas E, Dunfee R, Stanton J, Bogdan D, Kunstman K, Wolinsky S, et al. High frequency of defective vpu compared with tat and rev genes in brain from patients with HIV type 1-associated dementia. AIDS Res Hum Retroviruses. 2007;23:575-80 pubmed
    ..Here we analyzed sequences of tat, rev, and vpu genes in 55 subgenomic clones previously shown to encode functional env genes from brain and lymphoid tissues of four ..
  35. Gonzalez M, Carrasco L. Human immunodeficiency virus type 1 VPU protein affects Sindbis virus glycoprotein processing and enhances membrane permeabilization. Virology. 2001;279:201-9 pubmed
    ..Taken together, our data support the notion that HIV-1 Vpu and SV 6K proteins share some analogous functions. ..
  36. Nishino Y, Kishi M, Sumiya M, Ogawa K, Adachi A, Maotani Imai K, et al. Human immunodeficiency virus type 1 vif, vpr, and vpu mutants can produce persistently infected cells. Arch Virol. 1991;120:181-92 pubmed
    ..The HIV-1 particles produced from the surviving cells after infection with the vif, vpr, or vpu mutant viruses were fully replicative in M 10 cells without apparent cytopathic effects. ..
  37. Coutlee F, He Y, Saint Antoine P, Olivier C, Kessous A. Coamplification of HIV type 1 and beta-globin gene DNA sequences in a nonisotopic polymerase chain reaction assay to control for amplification efficiency. AIDS Res Hum Retroviruses. 1995;11:363-71 pubmed
    ..Nonisotopic coamplification allowed for the evaluation of the quality of specimens for PCR concurrently with the detection of the presence of viral template sequences. ..
  38. Siwka W, Schwinn A, Baczko K, Pardowitz I, Mhalu F, Shao J, et al. vpu and env sequence variability of HIV-1 isolates from Tanzania. AIDS Res Hum Retroviruses. 1994;10:1753-4 pubmed
    ..The variability of East African HIV-1 isolates are consistent with the view that these are rapidly changing viruses for which further variants are likely to be discovered. ..
  39. Geraghty R, Talbot K, Callahan M, Harper W, Panganiban A. Cell type-dependence for Vpu function. J Med Primatol. 1994;23:146-50 pubmed
    ..A yeast GAL4 transcriptional activation system was used to screen for cellular proteins that may interact with Vpu. One such protein was identified which we provisionally designate "Vpu interactive protein" or VIP. ..
  40. Mustafa F, Robinson H. Context-dependent role of human immunodeficiency virus type 1 auxiliary genes in the establishment of chronic virus producers. J Virol. 1993;67:6909-15 pubmed
    ..These results suggest that complex interactions of viral auxiliary and nonauxiliary gene functions with the host cell determine the ability to establish chronic virus producers. ..
  41. Vanden Haesevelde M, Peeters M, Jannes G, Janssens W, van der Groen G, Sharp P, et al. Sequence analysis of a highly divergent HIV-1-related lentivirus isolated from a wild captured chimpanzee. Virology. 1996;221:346-50 pubmed
    ..Our data suggest multiple introductions of HIV-1 in the human population and shed new light on the origin of the HIV-1 pandemic. ..
  42. Geleziunas R, Morin N, Wainberg M. [Mechanisms of reduction of CD4 receptor expression on the surface of HIV-1 infected cells]. C R Acad Sci III. 1996;319:653-62 pubmed
    ..Finally, CD4 which is retained by gp160 in the ER, is specifically degraded in the presence of Vpu. Thus, it appears that CD4 down-regulation is of central importance to the life cycle of HIV-1. ..
  43. Scriba T, Treurnicht F, Zeier M, Engelbrecht S, Van Rensburg E. Characterization and phylogenetic analysis of South African HIV-1 subtype C accessory genes. AIDS Res Hum Retroviruses. 2001;17:775-81 pubmed
    ..impact on vaccine strategies of HIV-1 subtype C in South Africa, we have characterized the vif, vpr, and vpu genes of 15 isolates...
  44. Mackay G, Niu Y, Liu Z, Mukherjee S, Li Z, Adany I, et al. Presence of Intact vpu and nef genes in nonpathogenic SHIV is essential for acquisition of pathogenicity of this virus by serial passage in macaques. Virology. 2002;295:133-46 pubmed
    ..The nef, LTR, and env of the SHIV(PPC) viruses underwent numerous mutations, compared to DeltavpuDeltanefSHIV(PPC). This study confirms the seminal role that nef, LTR, and vpu could play in regulation of pathogenesis of HIV infection. ..
  45. Song S, Li H, Cloyd M. Rates of shutdown of HIV-1 into latency: roles of the LTR and tat/rev/vpu gene region. Virology. 1996;225:377-86 pubmed
    ..It is also possible that this viral property may be an important determinant of clinical outcomes. ..
  46. Kishi M, Zheng Y, Bahmani M, Tokunaga K, Takahashi H, Kakinuma M, et al. Naturally occurring accessory gene mutations lead to persistent human immunodeficiency virus type 1 infection of CD4-positive T cells. J Virol. 1995;69:7507-18 pubmed
    ..Thus, mutations generating multiple accessory gene defects during HIV-1 replication correlate with viral persistence and loss of cytopathogenicity. ..
  47. Jeeninga R, Jan B, van der Linden B, van den Berg H, Berkhout B. Construction of a minimal HIV-1 variant that selectively replicates in leukemic derived T-cell lines: towards a new virotherapy approach. Cancer Res. 2005;65:3347-55 pubmed
    ..The mini-HIV variant that uses CD4 and CXCR4 for cell entry could potentially be used against CXCR4-expressing malignancies such as T-lymphoblastic leukemia/lymphoma, natural killer leukemia, and some myeloid leukemias. ..
  48. Hout D, Gomez L, Pacyniak E, Miller J, Hill M, Stephens E. A single amino acid substitution within the transmembrane domain of the human immunodeficiency virus type 1 Vpu protein renders simian-human immunodeficiency virus (SHIV(KU-1bMC33)) susceptible to rimantadine. Virology. 2006;348:449-61 pubmed
  49. Kishi M, Nishino Y, Sumiya M, Ohki K, Kimura T, Goto T, et al. Cells surviving infection by human immunodeficiency virus type 1: vif or vpu mutants produce non-infectious or markedly less cytopathic viruses. J Gen Virol. 1992;73 ( Pt 1):77-87 pubmed
    ..Thus, M10 cells surviving infection with HIV-1 vif or vpu mutants are heterogeneous, persistently expressing HIV-1 antigens and producing non-infectious or less cytopathic virus. ..
  50. Yao X, Gottlinger H, Haseltine W, Cohen E. Envelope glycoprotein and CD4 independence of vpu-facilitated human immunodeficiency virus type 1 capsid export. J Virol. 1992;66:5119-26 pubmed
    ..The vpu protein acts in trans to facilitate export of virus capsid proteins from HeLa cells. ..
  51. Lee C, Wang W, Fan W, Twu S, Chen S, Sheng M, et al. Determination of human immunodeficiency virus type 1 subtypes in Taiwan by vpu gene analysis. J Clin Microbiol. 2000;38:2468-74 pubmed
    ..Information on the vpu genes in the HIV sequence database is very limited...
  52. Li J, Halloran M, Lord C, Watson A, Ranchalis J, Fung M, et al. Persistent infection of macaques with simian-human immunodeficiency viruses. J Virol. 1995;69:7061-7 pubmed
    ..viruses (SHIV) containing the human immunodeficiency virus type 1 (HIV-1) tat, rev, env, and, in some cases, vpu genes were inoculated into eight cynomolgus monkeys...
  53. Nasioulas G, Paraskevis D, Magiorkinis E, Theodoridou M, Hatzakis A. Molecular analysis of the full-length genome of HIV type 1 subtype I: evidence of A/G/I recombination. AIDS Res Hum Retroviruses. 1999;15:745-58 pubmed
    ..Our results indicate that subtype I, which was probably circulating in Greece in the early 1980s, is a triple mosaic consisting of A, G, and I sequences. ..