Vpr of simian immunodeficiency virus of African green monkeys is required for replication in macaque macrophages and lymphocytes. (original) (raw)

• Journal List
• J Virol
• v.71(7); 1997 Jul
• PMC191801

J Virol. 1997 Jul; 71(7): 5593–5602.

Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH Twinbrook II Facility, Rockville, Maryland 20852, USA.

Abstract

The genomes of simian immunodeficiency viruses isolated from African green monkeys (SIVagm) contain a single accessory gene homolog of human immunodeficiency virus type 1 (HIV-1) vpr. This genomic organization differs from that of SIVsm-SIVmac-HIV-2 group viruses, which contain two gene homologs, designated vpr and vpx, which in combination appear to share the functions of HIV-1 vpr. The in vitro role of the SIVagm homolog was evaluated with molecularly cloned, pathogenic SIVagm9063-2. These studies revealed that this gene shares properties of HIV-1 vpr, such as nuclear and virion localization. In addition, SIVagm mutants with inactivating mutations of vpr are unable to replicate in nondividing cells, such as macaque monocyte-derived macrophages, but replicate to almost wild-type levels in a susceptible human T-cell line. The transport of virus preintegration complexes into the nucleus in primary macrophages, as measured by the production of unintegrated circular viral DNA, is less efficient for the mutant viruses than it is for the wild-type virus. SIVagm mutants also replicate inefficiently in primary macaque peripheral blood mononuclear cells, with a propensity for substitutions that remove the inserted inactivating stop codon. These data, in conjunction with recent findings that the Vpr protein is capable of inducing G2 arrest, are consistent with designation of this SIVagm accessory gene as vpr to reflect its shared functions and properties with HIV-1 vpr.

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Selected References

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• Balliet JW, Kolson DL, Eiger G, Kim FM, McGann KA, Srinivasan A, Collman R. 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 May 1;200(2):623–631. [PubMed] [Google Scholar]
• Bartz SR, Rogel ME, Emerman M. Human immunodeficiency virus type 1 cell cycle control: Vpr is cytostatic and mediates G2 accumulation by a mechanism which differs from DNA damage checkpoint control. J Virol. 1996 Apr;70(4):2324–2331. [PMC free article] [PubMed] [Google Scholar]
• Bouhamdan M, Benichou S, Rey F, Navarro JM, Agostini I, Spire B, Camonis J, Slupphaug G, Vigne R, Benarous R, et al. Human immunodeficiency virus type 1 Vpr protein binds to the uracil DNA glycosylase DNA repair enzyme. J Virol. 1996 Feb;70(2):697–704. [PMC free article] [PubMed] [Google Scholar]
• Bukrinsky MI, Sharova N, Dempsey MP, Stanwick TL, Bukrinskaya AG, Haggerty S, Stevenson M. Active nuclear import of human immunodeficiency virus type 1 preintegration complexes. Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6580–6584. [PMC free article] [PubMed] [Google Scholar]
• Bukrinsky MI, Haggerty S, Dempsey MP, Sharova N, Adzhubel A, Spitz L, Lewis P, Goldfarb D, Emerman M, Stevenson M. A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. Nature. 1993 Oct 14;365(6447):666–669. [PMC free article] [PubMed] [Google Scholar]
• Campbell BJ, Hirsch VM. Extensive envelope heterogeneity of simian immunodeficiency virus in tissues from infected macaques. J Virol. 1994 May;68(5):3129–3137. [PMC free article] [PubMed] [Google Scholar]
• Chackerian B, Haigwood NL, Overbaugh J. Characterization of a CD4-expressing macaque cell line that can detect virus after a single replication cycle and can be infected by diverse simian immunodeficiency virus isolates. Virology. 1995 Nov 10;213(2):386–394. [PubMed] [Google Scholar]
• Cohen EA, Terwilliger EF, Jalinoos Y, Proulx J, Sodroski JG, Haseltine WA. Identification of HIV-1 vpr product and function. J Acquir Immune Defic Syndr. 1990;3(1):11–18. [PubMed] [Google Scholar]
• Connor RI, Chen BK, Choe S, Landau NR. Vpr is required for efficient replication of human immunodeficiency virus type-1 in mononuclear phagocytes. Virology. 1995 Feb 1;206(2):935–944. [PubMed] [Google Scholar]
• Du Z, Lang SM, Sasseville VG, Lackner AA, Ilyinskii PO, Daniel MD, Jung JU, Desrosiers RC. Identification of a nef allele that causes lymphocyte activation and acute disease in macaque monkeys. Cell. 1995 Aug 25;82(4):665–674. [PubMed] [Google Scholar]
• Fletcher TM, 3rd, Brichacek B, Sharova N, Newman MA, Stivahtis G, Sharp PM, Emerman M, Hahn BH, Stevenson M. Nuclear import and cell cycle arrest functions of the HIV-1 Vpr protein are encoded by two separate genes in HIV-2/SIV(SM). EMBO J. 1996 Nov 15;15(22):6155–6165. [PMC free article] [PubMed] [Google Scholar]
• Freed EO, Englund G, Martin MA. Role of the basic domain of human immunodeficiency virus type 1 matrix in macrophage infection. J Virol. 1995 Jun;69(6):3949–3954. [PMC free article] [PubMed] [Google Scholar]
• Gallay P, Swingler S, Aiken C, Trono D. HIV-1 infection of nondividing cells: C-terminal tyrosine phosphorylation of the viral matrix protein is a key regulator. Cell. 1995 Feb 10;80(3):379–388. [PubMed] [Google Scholar]
• Gibbs JS, Lackner AA, Lang SM, Simon MA, Sehgal PK, Daniel MD, Desrosiers RC. Progression to AIDS in the absence of a gene for vpr or vpx. J Virol. 1995 Apr;69(4):2378–2383. [PMC free article] [PubMed] [Google Scholar]
• Gibbs JS, Regier DA, Desrosiers RC. Construction and in vitro properties of SIVmac mutants with deletions in "nonessential" genes. AIDS Res Hum Retroviruses. 1994 May;10(5):607–616. [PubMed] [Google Scholar]
• Guyader M, Emerman M, Montagnier L, Peden K. VPX mutants of HIV-2 are infectious in established cell lines but display a severe defect in peripheral blood lymphocytes. EMBO J. 1989 Apr;8(4):1169–1175. [PMC free article] [PubMed] [Google Scholar]
• He J, Choe S, Walker R, Di Marzio P, Morgan DO, Landau NR. Human immunodeficiency virus type 1 viral protein R (Vpr) arrests cells in the G2 phase of the cell cycle by inhibiting p34cdc2 activity. J Virol. 1995 Nov;69(11):6705–6711. [PMC free article] [PubMed] [Google Scholar]
• Heinzinger NK, Bukrinsky MI, Haggerty SA, Ragland AM, Kewalramani V, Lee MA, Gendelman HE, Ratner L, Stevenson M, Emerman M. The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7311–7315. [PMC free article] [PubMed] [Google Scholar]
• Hirsch VM, Dapolito G, Johnson PR, Elkins WR, London WT, Montali RJ, Goldstein S, Brown C. Induction of AIDS by simian immunodeficiency virus from an African green monkey: species-specific variation in pathogenicity correlates with the extent of in vivo replication. J Virol. 1995 Feb;69(2):955–967. [PMC free article] [PubMed] [Google Scholar]
• Hoch J, Lang SM, Weeger M, Stahl-Hennig C, Coulibaly C, Dittmer U, Hunsmann G, Fuchs D, Müller J, Sopper S, et al. vpr deletion mutant of simian immunodeficiency virus induces AIDS in rhesus monkeys. J Virol. 1995 Aug;69(8):4807–4813. [PMC free article] [PubMed] [Google Scholar]
• Hu W, Vander Heyden N, Ratner L. Analysis of the function of viral protein X (VPX) of HIV-2. Virology. 1989 Dec;173(2):624–630. [PubMed] [Google Scholar]
• Jowett JB, Planelles V, Poon B, Shah NP, Chen ML, Chen IS. The human immunodeficiency virus type 1 vpr gene arrests infected T cells in the G2 + M phase of the cell cycle. J Virol. 1995 Oct;69(10):6304–6313. [PMC free article] [PubMed] [Google Scholar]
• Kappes JC, Parkin JS, Conway JA, Kim J, Brouillette CG, Shaw GM, Hahn BH. Intracellular transport and virion incorporation of vpx requires interaction with other virus type-specific components. Virology. 1993 Mar;193(1):222–233. [PubMed] [Google Scholar]
• Kawamura M, Sakai H, Adachi A. Human immunodeficiency virus Vpx is required for the early phase of replication in peripheral blood mononuclear cells. Microbiol Immunol. 1994;38(11):871–878. [PubMed] [Google Scholar]
• Kestler HW, 3rd, Ringler DJ, Mori K, Panicali DL, Sehgal PK, Daniel MD, Desrosiers RC. Importance of the nef gene for maintenance of high virus loads and for development of AIDS. Cell. 1991 May 17;65(4):651–662. [PubMed] [Google Scholar]
• Kewalramani VN, Emerman M. Vpx association with mature core structures of HIV-2. Virology. 1996 Apr 1;218(1):159–168. [PubMed] [Google Scholar]
• Lang SM, Weeger M, Stahl-Hennig C, Coulibaly C, Hunsmann G, Müller J, Müller-Hermelink H, Fuchs D, Wachter H, Daniel MM, et al. Importance of vpr for infection of rhesus monkeys with simian immunodeficiency virus. J Virol. 1993 Feb;67(2):902–912. [PMC free article] [PubMed] [Google Scholar]
• Levy DN, Fernandes LS, Williams WV, Weiner DB. Induction of cell differentiation by human immunodeficiency virus 1 vpr. Cell. 1993 Feb 26;72(4):541–550. [PubMed] [Google Scholar]
• Levy DN, Refaeli Y, Weiner DB. Extracellular Vpr protein increases cellular permissiveness to human immunodeficiency virus replication and reactivates virus from latency. J Virol. 1995 Feb;69(2):1243–1252. [PMC free article] [PubMed] [Google Scholar]
• Liska V, Spehner D, Mehtali M, Schmitt D, Kirn A, Aubertin AM. Localization of viral protein X in simian immunodeficiency virus macaque strain and analysis of its packaging requirements. J Gen Virol. 1994 Nov;75(Pt 11):2955–2962. [PubMed] [Google Scholar]
• Lu YL, Spearman P, Ratner L. Human immunodeficiency virus type 1 viral protein R localization in infected cells and virions. J Virol. 1993 Nov;67(11):6542–6550. [PMC free article] [PubMed] [Google Scholar]
• Lu YL, Bennett RP, Wills JW, Gorelick R, Ratner L. A leucine triplet repeat sequence (LXX)4 in p6gag is important for Vpr incorporation into human immunodeficiency virus type 1 particles. J Virol. 1995 Nov;69(11):6873–6879. [PMC free article] [PubMed] [Google Scholar]
• Mahalingam S, Collman RG, Patel M, Monken CE, Srinivasan A. Functional analysis of HIV-1 Vpr: identification of determinants essential for subcellular localization. Virology. 1995 Oct 1;212(2):331–339. [PubMed] [Google Scholar]
• Marcon L, Michaels F, Hattori N, Fargnoli K, Gallo RC, Franchini G. Dispensable role of the human immunodeficiency virus type 2 Vpx protein in viral replication. J Virol. 1991 Jul;65(7):3938–3942. [PMC free article] [PubMed] [Google Scholar]
• Park IW, Sodroski J. Functional analysis of the vpx, vpr, and nef genes of simian immunodeficiency virus. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Apr 1;8(4):335–344. [PubMed] [Google Scholar]
• Paxton W, Connor RI, Landau NR. Incorporation of Vpr into human immunodeficiency virus type 1 virions: requirement for the p6 region of gag and mutational analysis. J Virol. 1993 Dec;67(12):7229–7237. [PMC free article] [PubMed] [Google Scholar]
• Planelles V, Jowett JB, Li QX, Xie Y, Hahn B, Chen IS. Vpr-induced cell cycle arrest is conserved among primate lentiviruses. J Virol. 1996 Apr;70(4):2516–2524. [PMC free article] [PubMed] [Google Scholar]
• Re F, Braaten D, Franke EK, 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 Nov;69(11):6859–6864. [PMC free article] [PubMed] [Google Scholar]
• Refaeli Y, Levy DN, Weiner DB. The glucocorticoid receptor type II complex is a target of the HIV-1 vpr gene product. Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3621–3625. [PMC free article] [PubMed] [Google Scholar]
• Sharp PM, Bailes E, Stevenson M, Emerman M, Hahn BH. Gene acquisition in HIV and SIV. Nature. 1996 Oct 17;383(6601):586–587. [PMC free article] [PubMed] [Google Scholar]
• Stivahtis GL, Soares MA, Vodicka MA, Hahn BH, Emerman M. Conservation and host specificity of Vpr-mediated cell cycle arrest suggest a fundamental role in primate lentivirus evolution and biology. J Virol. 1997 Jun;71(6):4331–4338. [PMC free article] [PubMed] [Google Scholar]
• Tristem M, Marshall C, Karpas A, Hill F. Evolution of the primate lentiviruses: evidence from vpx and vpr. EMBO J. 1992 Sep;11(9):3405–3412. [PMC free article] [PubMed] [Google Scholar]
• Trono D. HIV accessory proteins: leading roles for the supporting cast. Cell. 1995 Jul 28;82(2):189–192. [PubMed] [Google Scholar]
• Wang L, Mukherjee S, Jia F, Narayan O, Zhao LJ. Interaction of virion protein Vpr of human immunodeficiency virus type 1 with cellular transcription factor Sp1 and trans-activation of viral long terminal repeat. J Biol Chem. 1995 Oct 27;270(43):25564–25569. [PubMed] [Google Scholar]
• Westervelt P, Henkel T, Trowbridge DB, Orenstein J, Heuser J, Gendelman HE, Ratner L. Dual regulation of silent and productive infection in monocytes by distinct human immunodeficiency virus type 1 determinants. J Virol. 1992 Jun;66(6):3925–3931. [PMC free article] [PubMed] [Google Scholar]
• Wu X, Conway JA, Kim J, Kappes JC. Localization of the Vpx packaging signal within the C terminus of the human immunodeficiency virus type 2 Gag precursor protein. J Virol. 1994 Oct;68(10):6161–6169. [PMC free article] [PubMed] [Google Scholar]
• Yao XJ, Subbramanian RA, Rougeau N, Boisvert F, Bergeron D, Cohen EA. Mutagenic analysis of human immunodeficiency virus type 1 Vpr: role of a predicted N-terminal alpha-helical structure in Vpr nuclear localization and virion incorporation. J Virol. 1995 Nov;69(11):7032–7044. [PMC free article] [PubMed] [Google Scholar]
• Yu XF, Yu QC, Essex M, Lee TH. The vpx gene of simian immunodeficiency virus facilitates efficient viral replication in fresh lymphocytes and macrophage. J Virol. 1991 Sep;65(9):5088–5091. [PMC free article] [PubMed] [Google Scholar]

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