Viral Protein X

  • J. C. Kappes
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 193)

Abstract

Since the discovery of the human immunodeficiency viruses types 1 (HIV-1) and 2 (HIV-2) as the causative agents of acquired immunodeficiency syndrome (AIDS) (Barre-Sinoussi et al. 1983; Clavel et al. 1987; Papovic et al. 1984) and the isolation of related lentiviruses from several species of Old World monkeys, much has been learned about their biology and evolution. Based on genetic analysis, five distinct phylogenetic lineages of primate lentiviruses have now been identified: HIV-1/simian immunodeficiency virus (SIV)CPZ, HIV-2/SIVSM/SIVMAC, SIVAGM, SIVMND, and SIVSYK (for review see Johnson et al. 1991; Myers et al. 1992; Sharp et al. 1994). Like all retroviruses, primate lentiviruses are similar in structure and genomic organization. They contain gag, pol, and env genes that encode structural proteins essential for virion architecture (Gag), glycoproteins that enable the virus to recognize and infect its target (Env), and enzymatic proteins essential for processes of virus maturation, reverse transcription, and integration (Pol). While the genomic structure of all five lineages is conserved, differences exist in the composition of auxiliary genes: all five groups of viruses contain tat, rev, nef and vif all but SIVAGM contain vpr, only HIV-1/SIVSYK contains vpu, and only HIV-2/SIVSM/SIVMAC and SIVAGM viruses contain vpx (Cullen and Green 1990; Johnson et al. 1991). Primate lentiviruses have complex life cycles regulated by interactions of viral structural and accessory gene products as well as host factors (Cullen 1991). Viral accessory genes modulate replication, host cell tropism, chronic persistence, and pathogenicity. Defining the role of viral accessory genes is critical for understanding the natural history of infection and disease pathogenesis and thus represents a major goal in biomedical AIDS research. Moreover, knowledge of accessory protein function may facilitate the development of therapeutic and vaccine interventions. In this chapter the author reviews the present understanding of the role of Vpx in the HIV-2/SIV life cycle and the structure-function relationships that mediate incorporation of this protein into virions. Based on genetic and phylogenetic evidence indicating that in the HIV-2/ SIVSM/SIVMAC lineage vpxarose from a gene duplication of vpr and on the proposed reclassification of SIVAGM vpx to vpr (Tristem et al. 1990, 1992), for clarity this review will discuss vpx for only the HIV-2/SIVSM/SIVMAC group of viruses.

Keywords

HPLC Resi Parkin Retro Virus Vaccinia 

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References

  1. Akari H, Sakuragi J, Takebe Y, Tomonaga K, Kawamura M, Fukasawa M, Miura T, Shinjo T, Hayami M (1992) Biological characterization of human immunodeficiency virus type 1 and type 2 mutants in human peripheral blood mononuclear cells. Arch Virol 123: 157–167PubMedCrossRefGoogle Scholar
  2. Arrigo SJ, Chen ISY (1991) Rev is necessary for translation but not cytoplasmic accumulation of HIV-1 vif, vpr and env/vpu 2 RNAs. Genes Dev 5: 808–819PubMedCrossRefGoogle Scholar
  3. Barre-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Giuest J, Dauguet C, Axler-Blin C, Vezinet-Brun F, Rouzioux C, Rozenbaum W, Montagnier L (1983) Isolation of a T-lymphotropic retrovirus from at patient at risk for acquired immune deficiency syndrome (AIDS). Science 220: 868–870PubMedCrossRefGoogle Scholar
  4. Chakrabarti L, Guyader M, Alizon M, Daniel MD, Desrosiers RC, Tiollais P, Sonigo P (1987) Sequence of simian immunodeficiency virus from macaque and its relationship to other human and simian retroviruses. Nature 328: 543–547PubMedCrossRefGoogle Scholar
  5. Clavel F, Mansinho K, Chamaret S, Guetard D, Favier V, Nina J, Santos-Ferreira M-D, Champalimaud J-L, Montagnier L (1987) Human immunodeficiency virus type 2 infection associated with AIDS in West Africa. N Engl J Med 316: 1180–1185PubMedCrossRefGoogle Scholar
  6. Cohen EA, Dehni G, Sodroski JG, Haseltine WA (1990a) Human immunodeficiency virus vpr product is a virion-associated regulatory protein. J Virol 64: 3097–3099PubMedGoogle Scholar
  7. Cohen EA, Terwilliger EF, Jalinoos Y, Proulx J, Sodroski JG, Haseltine WA (1990b) Identification of HIV-1 Vpr product and function. JAIDS 3: 11–18Google Scholar
  8. Cullen BR (1991) Human immunodeficiency virus as a prototypic complex retrovirus. J Virol 65: 1053–1056PubMedGoogle Scholar
  9. Cullen BR, Green WC (1990) Functions of the auxiliary gene products of the human immunodeficiency virus type 1. Virology 178: 1–5PubMedCrossRefGoogle Scholar
  10. Dedera D, Hu W, Vander-Hyden N, Ratner L (1989) Viral protein R of human immunodeficiency virus types 1 and 2 is dispensable for replication cytopathogenicity in lymphoid cells. J Virol 63: 3205–3208PubMedGoogle Scholar
  11. Dong J, Hunter E (1993) Analysis of retroviral assembly using a vaccinia/T7-polymerase complementation system. Virology 194: 192–199PubMedCrossRefGoogle Scholar
  12. Franchini G, Gurgo C, Guo H-G, Gallo RC, Collalti E, Fargnoli KA, Hall LF, Wong-Staal F, Reitz MS Jr (1987) Sequence of simian immunodeficiency virus and its relationship to the human immunodeficiency viruses. Nature 328: 539–542PubMedCrossRefGoogle Scholar
  13. Franchini G, Rusche JR, O’Keeffe TJ, Wong-Staal F (1988) The human immunodeficiency virus type 2 (HIV-2) contains a novel gene encoding a 16 kDa protein associated with mature virions. AIDS Res Hum Retro Viruses 4: 243–250CrossRefGoogle Scholar
  14. Fuerst RT, Niles EG, Studier W, Moss B (1986) Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase. Proc Natl Acad Sci USA 83: 8122–8126PubMedCrossRefGoogle Scholar
  15. Fuerst RT, Earl PL, Moss B (1987) Use of a hybrid vaccinia virus-T7 RNA polymerase system for expression of target genes. Mol Cell Biol 7: 2538–2544PubMedGoogle Scholar
  16. Garette ED, Tiley JS, Cullen BR (1991) Rev activates expression of the human immunodeficiency virus type 1 vif and vpr gene products. J Virol 65: 1653–1657Google Scholar
  17. Gelderblom HR (1991) Assembly and morphology of HIV: potential effects of structure on viral function. AIDS 5: 617–638PubMedCrossRefGoogle Scholar
  18. Gibbs JS, Regier DA, Desrosiers RC (1994) Construction and in vitro properties of SIVMAC mutants with deletions “in nonessential” genes. AIDS Res Hum Retro Viruses 10: 607–616CrossRefGoogle Scholar
  19. Guyader M, Emerman M, Sonigo P, Clavel F, Montagnier L, Alizon M (1987) Genome organization and transactivation of the human immunodeficiency virus type 2. Nature 326: 662–669PubMedCrossRefGoogle Scholar
  20. Guyader M, Emerman M, Montagnier L, Peden K (1989) Vpx mutants of HIV-2 are infectious in established cell lines but display a severe defect in peripheral blood lymphocytes. EMBO J 8: 1169–1175PubMedGoogle Scholar
  21. Hattori N, Michaels F, Fargnoli K, Marcon L, Gallo RC, Franchini G (1990) The human immunodeficiency virus type 2 Vpr gene is essential for productive infection of human macrophages. Proc Natl Acad Sci USA 87: 8080–8084PubMedCrossRefGoogle Scholar
  22. Henderson LE, Benveniste RE, Sowder R, Copeland TD, Schultz AM, Oroszlan S (1988a) Molecular characterization of gag proteins from simian immunodeficiency virus (SIVMne). J Virol 62: 2587–2595PubMedGoogle Scholar
  23. Henderson LE, Sowder RC, Copeland TD, Benveniste RE, Oroszlan S (1988b) Isolation and characterization of a novel protein (X-ORF product) from SIV and HIV-2. Science 241: 199–201PubMedCrossRefGoogle Scholar
  24. Horton R, Spearman P, Ratner L (1994) HIV-2 viral protein X associates with the Gag p27 capsid protein. Virology 199: 453–457PubMedCrossRefGoogle Scholar
  25. Hu W, Vander-Heyden N, Ratner L (1989) Analysis of the function of the viral protein X (VPX) of HIV-2. Virology 173: 624–630PubMedCrossRefGoogle Scholar
  26. Johnson PR, Myers G, Hirsch VM (1991) Genetic diversity and phylogeny of non-human primate lentiviruses. In: Koff WC, Wong-Staal F, Kennedy RC (eds) AIDS research reviews, vol 1. Dekker, New York; pp 47–62Google Scholar
  27. Jones MK, Anantharamaiah GM, Segrest JP (1992) Computer programs to identify and classify amphipathic alpha helical domains. J Lipid Res 33: 287–296PubMedGoogle Scholar
  28. Kappes JC, Parkin JS, Conway JA, Kim J, Brouillette CG, Shaw GM, Hahn BH (1993) Intracellular transport and virion incorporation of vpx requires interaction with other virus type-specific components. Virology 193: 222–233PubMedCrossRefGoogle Scholar
  29. Kappes JC, Conway JA, Lee S-VV, Shaw GM, Hahn BH (1991) Human immunodeficiency virus type 2 vpx protein augments viral infectivity. Virology 184: 197–209PubMedCrossRefGoogle Scholar
  30. Kappes JC, Morrow CD, Lee S-W, Jameson BA, Kent SB, Hood LE, Shaw GM, Hahn BH (1988) Identification of a novel retroviral gene unique to human immunodeficiency virus type 2 and simian immunodeficiency virus SIVMAC. J Virol 62: 3501–3505PubMedGoogle Scholar
  31. Kumar P, Hui H, Kappes JC, Haggarty BS, Hoxie JA, Arya SK, Shaw GM, Hahn BH (1990) Molecular characterization of an attenuated human immunodeficiency virus type 2 isolate. J Virol 64: 890–891PubMedGoogle Scholar
  32. Lavallée C, Yao XJ, Ladha A, Gottlinger H, Haseltine WA, Cohen EA (1994) Requirement of the Pr55gag precursor for incorporation of the Vpr product into human immunodeficiency virus type 1 viral particles. J Virol 68: 1926–1934PubMedGoogle Scholar
  33. Lu Y-L, Spearman P, Ratner L (1993) Human immunodeficiency virus type 1 viral protein R localization in infected cells and virions. J Virol 67: 6542–6550PubMedGoogle Scholar
  34. Marcon L, Michaels F, Hattori N, Fargnoli K, Gallo RC, Franchini G (1991) Dispensable role of the human immunodeficiency virus type 2 Vpx protein in viral replication. J Virol 65: 3938–3942PubMedGoogle Scholar
  35. Myers G, Maclnnes K, Korber B (1992) The emergence of simian/human immunodeficiency viruses. AIDS Res Hum Retro viruses 8: 373–386CrossRefGoogle Scholar
  36. Natsoulis G, Boeke JD (1991) New antiviral strategy using capsid-nuclease fusion proteins. Nature 352: 632–635PubMedCrossRefGoogle Scholar
  37. Ogawa K, Shibata R, Kiyomasu T, Higuchi I, Kishida Y, Ishimoto A, Adachi A (1989) Mutational analysis of the human immunodeficiency virus vpr open reading frame. J Virol 63: 4110–4114PubMedGoogle Scholar
  38. Papovic M, Sarngadharan MG, Read E, Gallo RC (1984) Detection, isolation and continuous culture production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science 224: 497–500CrossRefGoogle Scholar
  39. Paxton W, Conner RI, Landau NR (1993) Incorporation of Vpr into human immunodeficiency virus type 1 virions: requirement for the p6 regions of gag and mutational analysis. J Virol 67: 7229–7237PubMedGoogle Scholar
  40. Ratner L, Haseltine W, Patarca R, Livak KJ, Starcich B, Josephs SF, Doran ER, Rafalski JA, Whitehorn EA, Baumeister K, Ivanoff L, Petteway SR Jr, Pearson ML, Lautenberger JA, Papas TS, Ghrayeb J, Chang NT, Gallo RC and Wong- Staal F (1985) Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature 313: 277–284PubMedCrossRefGoogle Scholar
  41. Segrest JP, De Loof H, Dohlman JG, Brouillette CG, Anantharamaiah GM (1990) Amphipathic helix motif: classes and properties. Proteins Struct Funct Genet 8: 103–117PubMedCrossRefGoogle Scholar
  42. Sharp PM, Robertson DL, Gao F, Hahn BH (1994) Origins and diversity of human immunodeficiency viruses. AIDS 8 [Suppl]: S27–S42Google Scholar
  43. Shibata R, Miura T, Hayami M, Ogawa K, Sakai H, Kiyomasu T, Ishimoto A, Adachi A (1990) Mutational analysis of the human immunodeficiency virus type 2 (HIV-2) genome in relation to HIV-1 and simian immunodeficiency virus SIVAGM. J Virol 64: 742–747PubMedGoogle Scholar
  44. Tristem M, Marshall C, Karpas A, Petrik J, Hill F (1990) Origin of vpx in lentiviruses. Nature 347:341–342PubMedCrossRefGoogle Scholar
  45. Tristem M, Marshal C, Karpas A, Hill F (1992) Evolution of the primate lentiviruses: evidence from vpx and vpr. EMBO J 11: 3405–3412PubMedGoogle Scholar
  46. Venet A, Bourgault I, Aubertin A-M, Kieny M-P, Levy J-P (1992) Cytotoxic T lymphocyte response against multiple simian immunodeficiency virus (SIV) Proteins in SIV-infected macaques. J Immunol 148: 2899–2908PubMedGoogle Scholar
  47. Viglianti GA, Sharma PL, Mullilns JI (1990) Simian immunodeficiency virus displays complex patterns of RNA splicing. J Virol 64: 4207–4216PubMedGoogle Scholar
  48. Wain-Hobson S, Sonigo P, Danos O, Cole S, Alizon M (1985) Nucleotide sequence of the AIDS virus, LAV. Cell 40: 9–17PubMedCrossRefGoogle Scholar
  49. Westervelt P, Henkel, T, Trowbridge DB, Orenstein J, Heuser J, Gendelman HE, Ratner L (1992) Dual regulation of silent and productive infection in monocytes by distinct human immunodeficiency virus type 1 determinants. J Virol 66: 3925–3931PubMedGoogle Scholar
  50. Wu X, Boeke JD, Natsoulis G, Hahn BH, Kappes JC (1993) HIV/SIV virion associated accessory genes mediate efficient packaging of nuclease fusion proteins into the virus particle. Presented at the 1st National conference on human retroviruses and related infections, Washington DCGoogle Scholar
  51. Wu X, Kappes JC (1993) Identification of a nuclear targeting signal within the human immunodeficiency virus type-2 Vpx protein. Presented at the 1993 Cold Spring Harbor Laboratory symposium on retrovirusesGoogle Scholar
  52. Wu X, Conway JA, Kim J, Kappes JC (1994) Localization of the Vpx packaging signal within the C-terminus of the HIV-2 Gag Precursor protein. J Virol 68: (in press)Google Scholar
  53. Yu X-F, Ito S, Essex M, Lee T-H (1988) A naturally immunogenic virion-associated protein specific for HIV-2 and SIV. Nature 335: 262–265PubMedCrossRefGoogle Scholar
  54. Yu X-F, Yu Q-C, Essex M, Lee T-H (1991) The vpx gene of simian immunodeficiency virus facilitates efficient viral replication in fresh lymphocytes and macrophages. J Virol 65: 5088–5091PubMedGoogle Scholar
  55. Yu X-F, Matsuda Z, Yu Q-C, Lee T-H, Essex M (1993) Vpx of Simian immunodeficiency virus is localized primarily outside the virus core in mature virions. J Virol 67: 4386–4390PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • J. C. Kappes
    • 1
  1. 1.Departments of Medicine and MicrobiologyUniversity of Alabama at BirminghamBirminghamUSA

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