vpr genes


Summary: DNA sequences that form the coding region for a trans-activator protein that specifies rapid growth in human immunodeficiency virus (HIV). vpr is short for viral protein R, where R is undefined.

Top Publications

  1. Schröfelbauer B, Hakata Y, Landau N. HIV-1 Vpr function is mediated by interaction with the damage-specific DNA-binding protein DDB1. Proc Natl Acad Sci U S A. 2007;104:4130-5 pubmed
    ..The interaction with DDB1 may explain several of the diverse biological functions of Vpr and suggests potential roles for Vpr in HIV-1 replication. ..
  2. Somasundaran M, Sharkey M, Brichacek B, Luzuriaga K, Emerman M, Sullivan J, et al. Evidence for a cytopathogenicity determinant in HIV-1 Vpr. Proc Natl Acad Sci U S A. 2002;99:9503-8 pubmed
    ..This study suggests the presence of a determinant of in vivo cytopathogenicity within HIV-1 Vpr and further indicates that viral replication can be uncoupled from cytopathicity in vitro and in vivo. ..
  3. Mansky L. The mutation rate of human immunodeficiency virus type 1 is influenced by the vpr gene. Virology. 1996;222:391-400 pubmed
    ..Immunoprecipitation analysis indicated that Vpr virion incorporation coincided with the influence of vpr on the mutation rate. ..
  4. Poon B, Jowett J, Stewart S, Armstrong R, Rishton G, Chen I. Human immunodeficiency virus type 1 vpr gene induces phenotypic effects similar to those of the DNA alkylating agent, nitrogen mustard. J Virol. 1997;71:3961-71 pubmed
    ..These results are consistent with the hypothesis that Vpr induces G2 arrest through pathways that are similar to those utilized by DNA-damaging agents. ..
  5. Chen R, Le Rouzic E, Kearney J, Mansky L, Benichou S. Vpr-mediated incorporation of UNG2 into HIV-1 particles is required to modulate the virus mutation rate and for replication in macrophages. J Biol Chem. 2004;279:28419-25 pubmed
    ..g. viral DNA synthesis, that is essential for replication of human immunodeficiency virus type 1 in nondividing cells. ..
  6. Le Rouzic E, Benichou S. The Vpr protein from HIV-1: distinct roles along the viral life cycle. Retrovirology. 2005;2:11 pubmed
    ..In this review, we will mainly focus on vpr from HIV-1 and discuss the most recent developments in our understanding of Vpr functions and its role during the virus replication cycle. ..
  7. Gragerov A, Kino T, Ilyina Gragerova G, Chrousos G, Pavlakis G. HHR23A, the human homologue of the yeast repair protein RAD23, interacts specifically with Vpr protein and prevents cell cycle arrest but not the transcriptional effects of Vpr. Virology. 1998;245:323-30 pubmed
    ..Therefore, a simple sequestering model for Vpr in the presence of excess HHR23A is not supported. We propose that the interaction of HHR23A with Vpr may affect specifically pathways leading to cell cycle regulation. ..
  8. Shen C, Gupta P, Wu H, Chen X, Huang X, Zhou Y, et al. Molecular characterization of the HIV type 1 vpr gene in infected Chinese former blood/plasma donors at different stages of diseases. AIDS Res Hum Retroviruses. 2008;24:661-6 pubmed publisher
    ..These results show that vpr may not play an important role in HIV-1 pathogenesis in different stages of Chinese patients and may have important implications in developing vpr-related treatments suitable for HIV-1-infected PBDs. ..
  9. Jowett J, Planelles V, Poon B, Shah N, Chen M, Chen I. The human immunodeficiency virus type 1 vpr gene arrests infected T cells in the G2 + M phase of the cell cycle. J Virol. 1995;69:6304-13 pubmed
    ..Cell cycle arrest induced by Vpr correlates with an increase in the hyperphosphorylated (inactive) form of the cyclin-dependent serine/threonine kinase CDC2, consistent with an arrest of cells at the boundary of G2 and M. ..

More Information


  1. Re F, Braaten D, Franke E, Luban J. Human immunodeficiency virus type 1 Vpr arrests the cell cycle in G2 by inhibiting the activation of p34cdc2-cyclin B. J Virol. 1995;69:6859-64 pubmed
    ..These studies demonstrate that HIV-1 vpr has profound effects on the cellular factors which control entry into mitosis and indicate vpr's potential contribution to the cellular pathology associated with HIV-1 infection. ..
  2. Mologni D, Citterio P, Menzaghi B, Zanone Poma B, Riva C, Broggini V, et al. Vpr and HIV-1 disease progression: R77Q mutation is associated with long-term control of HIV-1 infection in different groups of patients. AIDS. 2006;20:567-74 pubmed
    ..The R77Q mutation might reduce CD4+ T-cell depletion possibly affecting T-cell survival in vivo by altering the pro-apoptotic activity of Vpr. ..
  3. Hughes A, Westover K, da Silva J, O connor D, Watkins D. Simultaneous positive and purifying selection on overlapping reading frames of the tat and vpr genes of simian immunodeficiency virus. J Virol. 2001;75:7966-72 pubmed
  4. Rajan D, Wildum S, Rücker E, Schindler M, Kirchhoff F. Effect of R77Q, R77A and R80A changes in Vpr on HIV-1 replication and CD4 T cell depletion in human lymphoid tissue ex vivo. AIDS. 2006;20:831-6 pubmed
  5. Poon B, Chen I. Human immunodeficiency virus type 1 (HIV-1) Vpr enhances expression from unintegrated HIV-1 DNA. J Virol. 2003;77:3962-72 pubmed
    ..These results attribute a new function to HIV-1 Vpr and implicate Vpr as a critical component in expression from unintegrated HIV-1 DNA...
  6. Tristem M, Purvis A, Quicke D. Complex evolutionary history of primate lentiviral vpr genes. Virology. 1998;240:232-7 pubmed
  7. Bouzar A, Guiguen F, Morin T, Villet S, Fornazero C, Garnier C, et al. Specific G2 arrest of caprine cells infected with a caprine arthritis encephalitis virus expressing vpr and vpx genes from simian immunodeficiency virus. Virology. 2003;309:41-52 pubmed
    ..The data presented here thus raise a pertinent question about the biological significance of the conservation of Vpr and Vpx functions in caprine cells despite the high phylogenic distance between primates and small ruminants...
  8. Zhu Y, Gelbard H, Roshal M, Pursell S, Jamieson B, Planelles V. Comparison of cell cycle arrest, transactivation, and apoptosis induced by the simian immunodeficiency virus SIVagm and human immunodeficiency virus type 1 vpr genes. J Virol. 2001;75:3791-801 pubmed
    ..Taken together, our results suggest that while the multiple functions of vpr are conserved between HIV-1 and SIVagm, the mechanisms leading to the execution of such functions are divergent. ..
  9. Zhao Y, Cao J, O Gorman M, Yu M, Yogev R. Effect of human immunodeficiency virus type 1 protein R (vpr) gene expression on basic cellular function of fission yeast Schizosaccharomyces pombe. J Virol. 1996;70:5821-6 pubmed
    ..Together, these data showed that the HIV-1 Vpr-induced cellular changes in S. pombe are similar to those observed in human cells. Therefore, the S. pombe system is suited for further investigation of the HIV-1 vpr gene functions. ..
  10. 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. ..
  11. Andersen J, Planelles V. The role of Vpr in HIV-1 pathogenesis. Curr HIV Res. 2005;3:43-51 pubmed
    ..This review presents the latest findings about the pathogenic events triggered by Vpr, the cellular pathways involved, and the molecular and cellular consequences of the action of Vpr in the context of HIV-1 infection. ..
  12. Bano A, Gupta N, Sharma Y, Sood V, Banerjea A. HIV-1 VprB and C RNA cleavage by potent 10-23 DNAzymes that also cause reversal of G2 cell cycle arrest mediated by Vpr genes. Oligonucleotides. 2007;17:465-72 pubmed
    ..Thus, Dz-94 could potentially be developed to prevent Vpr-mediated cytopathic effects caused by HIV-1 subtype B and C isolates. ..
  13. Di Marzio P, Choe S, Ebright M, Knoblauch R, Landau N. Mutational analysis of cell cycle arrest, nuclear localization and virion packaging of human immunodeficiency virus type 1 Vpr. J Virol. 1995;69:7909-16 pubmed
    ..We speculate that Vpr has two sites for interaction with cellular factors: one in the alpha-helical region that specifies nuclear localization and one in the carboxy-terminal domain that is required for Cdc2 inhibition. ..
  14. Zhao L, Mukherjee S, Narayan O. Biochemical mechanism of HIV-I Vpr function. Specific interaction with a cellular protein. J Biol Chem. 1994;269:15577-82 pubmed
    ..These results suggest that RIP may be involved in Vpr function. ..
  15. Cali L, Wang B, Mikhail M, Gill M, Beckthold B, Salemi M, et al. Evidence for host-driven selection of the HIV type 1 vpr gene in vivo during HIV disease progression in a transfusion-acquired cohort. AIDS Res Hum Retroviruses. 2005;21:728-33 pubmed
  16. Park I, Myrick K, Sodroski J. Effects of vif mutations on cell-free infectivity and replication of simian immunodeficiency virus. J Acquir Immune Defic Syndr. 1994;7:1228-36 pubmed
    ..The effects of two different point mutations in vif were examined. One point mutant in vif reverted to the genetic sequence of the wild-type virus within 2 weeks.2 + ..
  17. Zuo Y, Matsusaka T, Zhong J, Ma J, Ma L, Hanna Z, et al. HIV-1 genes vpr and nef synergistically damage podocytes, leading to glomerulosclerosis. J Am Soc Nephrol. 2006;17:2832-43 pubmed
    ..In contrast, all vpr or nef single-transgenic mice in the same litter uniformly showed no or much milder podocyte injury. These findings indicate that vpr and nef each can induce podocyte injury with a prominent synergistic interaction...
  18. Muta T. [Biological defense mechanism common to all multi-cellular organisms]. Fukuoka Igaku Zasshi. 2002;93:172-7 pubmed
  19. 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. ..
  20. Ueno F, Shiota H, Miyaura M, Yoshida A, Sakurai A, Tatsuki J, et al. Vpx and Vpr proteins of HIV-2 up-regulate the viral infectivity by a distinct mechanism in lymphocytic cells. Microbes Infect. 2003;5:387-95 pubmed
  21. 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. ..
  22. Nakaya T, Fujinaga K, Kishi M, Oka S, Kurata T, Jones I, et al. Nonsense mutations in the vpr gene of HIV-1 during in vitro virus passage and in HIV-1 carrier-derived peripheral blood mononuclear cells. FEBS Lett. 1994;354:17-22 pubmed
    ..These data are consistent with a mechanism of HIV-1 persistence in vivo and in vitro in which virus cytopathogenic potential is lost by the build up of nonsense mutations in vpr. ..
  23. 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. ..
  24. Wan J, Ratner L. Effects of mutant Vpr/Vpx on HIV-2 assembly demonstrated by immunoelectron microscopy. Proc Natl Sci Counc Repub China B. 2001;25:50-8 pubmed
    ..These results provide evidence that Vpr or Vpr/Vpx mutants reduce RT activity and interfere with the expression of Vpx in HIV-2 particles during viral assembly. Vpr is efficient for Vpx corporation during viral assembly. ..
  25. Bent A, Mackey D. Elicitors, effectors, and R genes: the new paradigm and a lifetime supply of questions. Annu Rev Phytopathol. 2007;45:399-436 pubmed
    ..The present review uses numerous questions to help clarify what we know and to identify areas that are ripe for further investigation. ..
  26. Haga T, Okoba M, Yamazaki N, Kumabe S, Shimizu Y, Goto Y, et al. Characterization of vpr vector constructed from chimeric simian and human immunodeficiency virus. J Vet Med Sci. 2003;65:633-6 pubmed
    ..These results suggest that the length of the insert is an important factor for the replication ability of SHIV-3sj vector. ..
  27. 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. ..
  28. Brooks D, Cohen M, Jamieson B, Poon B, Kitchen S, Chow S, et al. Rapid size dependent deletion of foreign gene sequences inserted into attenuated HIV-1 upon infection in vivo: implications for vaccine development. Curr HIV Res. 2005;3:377-92 pubmed
    ..Moreover, NL-TKI reporter virus with both intact nef and vpr genes shows deletion of TK gene both in vitro and in vivo...
  29. Rodes B, Toro C, Paxinos E, Poveda E, Martinez Padial M, Benito J, et al. Differences in disease progression in a cohort of long-term non-progressors after more than 16 years of HIV-1 infection. AIDS. 2004;18:1109-16 pubmed
    ..A substantial proportion of LTNP show low-level virus replication and progressive loss of CD4 T cells over time. Progressive immunologic damage seems to be directly associated with some degree of virus replication and T-cell activation. ..
  30. Warren R, Merritt P, Holub E, Innes R. Identification of three putative signal transduction genes involved in R gene-specified disease resistance in Arabidopsis. Genetics. 1999;152:401-12 pubmed
    ..The pbs mutations are recessive and have been mapped to chromosomes I (pbs2) and V (pbs1 and pbs3). ..
  31. Muthumani K, Kudchodkar S, Papasavvas E, Montaner L, Weiner D, Ayyavoo V. HIV-1 Vpr regulates expression of beta chemokines in human primary lymphocytes and macrophages. J Leukoc Biol. 2000;68:366-72 pubmed
    ..These results suggest that a Vpr-mediated increase in virus replication could be in part through down-regulation of chemokine production. ..
  32. Kawano Y, Tanaka Y, Misawa N, Tanaka R, Kira J, Kimura T, et al. Mutational analysis of human immunodeficiency virus type 1 (HIV-1) accessory genes: requirement of a site in the nef gene for HIV-1 replication in activated CD4+ T cells in vitro and in vivo. J Virol. 1997;71:8456-66 pubmed
    ..These results indicate that Nef accelerates viral replication in activated CD4+ T cells. ..
  33. 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. ..
  34. Suzuki Y, Misawa N, Sato C, Ebina H, Masuda T, Yamamoto N, et al. Quantitative analysis of human immunodeficiency virus type 1 DNA dynamics by real-time PCR: integration efficiency in stimulated and unstimulated peripheral blood mononuclear cells. Virus Genes. 2003;27:177-88 pubmed
    ..Therefore, our assay is useful for analyzing the events in early phase of HIV-1 infection under various conditions. ..
  35. 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. ..
  36. Benko Z, Liang D, Agbottah E, Hou J, Taricani L, Young P, et al. Antagonistic interaction of HIV-1 Vpr with Hsf-mediated cellular heat shock response and Hsp16 in fission yeast (Schizosaccharomyces pombe). Retrovirology. 2007;4:16 pubmed
    ..These data suggest that fission yeast could be used as a model to further delineate the potential dynamic and antagonistic interactions between HIV-1 Vpr and cellular heat shock responses involving Hsps. ..
  37. Janket M, DeRicco J, Borowski L, Ayyavoo V. Human immunodeficiency virus (HIV-1) Vpr induced downregulation of NHE1 induces alteration in intracellular pH and loss of ERM complex in target cells. Virus Res. 2007;126:76-85 pubmed
    ..Vpr-mediated NHE1 dyregulation is in part through GR pathway as GR antagonist, mifepristone reversed Vpr-induced NHE1 downregulation. ..
  38. Gibbs J, Regier D, Desrosiers R. Construction and in vitro properties of SIVmac mutants with deletions in "nonessential" genes. AIDS Res Hum Retroviruses. 1994;10:333-42 pubmed
  39. Srinivasakumar N. HIV-1 vector systems. Somat Cell Mol Genet. 2001;26:51-81 pubmed
    ..This is a rapidly advancing field that with further refinements may soon allow the utilization of HIV-1 based and/or other lentivirus vectors in a clinical setting. ..
  40. 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
  41. 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. ..
  42. Srinivasan A, Ayyavoo V, Mahalingam S, Kannan A, Boyd A, Datta D, et al. A comprehensive analysis of the naturally occurring polymorphisms in HIV-1 Vpr: potential impact on CTL epitopes. Virol J. 2008;5:99 pubmed publisher
    ..The available data on naturally occurring polymorphisms will be useful to assess their potential effect on the structural and functional constraints of Vpr and also on the fitness of HIV-1 for replication. ..
  43. Smolen G, Schott B, Stewart R, Diederichs S, Muir B, Provencher H, et al. A Rap GTPase interactor, RADIL, mediates migration of neural crest precursors. Genes Dev. 2007;21:2131-6 pubmed
    ..We specifically show that these defects are primarily due to the diminished migratory capacity of NC cells. The identification of RADIL as a regulator of NC migration defines a role for the Rap pathway in this process. ..
  44. 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. ..
  45. Tao Y, Xie Z, Chen W, Glazebrook J, Chang H, Han B, et al. Quantitative nature of Arabidopsis responses during compatible and incompatible interactions with the bacterial pathogen Pseudomonas syringae. Plant Cell. 2003;15:317-30 pubmed
    ..This finding is consistent with the resistance phenotypes of these plants. We propose a simple quantitative model with a saturating response curve that approximates the overall behavior of this plant-pathogen system. ..
  46. 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. ..
  47. 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...
  48. Villet S, Bouzar B, Morin T, Verdier G, Legras C, Chebloune Y. Maedi-visna virus and caprine arthritis encephalitis virus genomes encode a Vpr-like but no Tat protein. J Virol. 2003;77:9632-8 pubmed
    ..8-fold. Together, these data strongly suggest that the tat ORF in the SRLV genomes does not code for a regulatory transactivator of the LTR but, rather, for a Vpr-like accessory protein...
  49. 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. ..
  50. 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. ..
  51. Abimiku A, Franchini G, Aldrich K, Myagkikh M, Markham P, Gard E, et al. Humoral and cellular immune responses in rhesus macaques infected with human immunodeficiency virus type 2. AIDS Res Hum Retroviruses. 1995;11:383-93 pubmed
    ..Elucidation of immune correlates of vaccine protection may therefore require sampling of lymphoid tissues and assessment of enriched CD8+ populations. ..
  52. Matsuda Z, Yu X, Yu Q, Lee T, Essex M. A virion-specific inhibitory molecule with therapeutic potential for human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1993;90:3544-8 pubmed
    ..This demonstrates the therapeutic potential of an accessory gene-based virion-specific inhibitory molecule. Vpx and its derivatives can be regarded as a new class of anti-HIV-1 molecule. ..
  53. Ratner L, Vander Heyden N, Garcia J, Polinsky M, Westervelt P, Becich M. Formation of noninfectious HIV-1 virus particles lacking a full-length envelope protein. AIDS Res Hum Retroviruses. 1991;7:287-94 pubmed
    ..Isogenic pairs of env deletion clones were produced with or without an additional deletion in the vif and vpr genes. Upon transfection, all clones produced virus particles, as determined by p24 antigen, reverse transcriptase, ..