1887

Abstract

The proteolytic processing of human immunodeficiency virus (HIV) particles mediated by the viral -encoded protease (PR) is essential for viral infectivity. The coding sequence partially overlaps with the coding sequence and is translated as a Gag–Pol polyprotein precursor. Within Gag–Pol, the C-terminal p6 domain is replaced by a transframe peptide referred to as p6*, which separates the Gag nucleocapsid domain from PR. Several previous studies have ascribed a PR-suppression regulatory function to p6*. Here, it was demonstrated that an HIV-1 Gag–Pol lacking p6* is efficiently incorporated into virions when coexpressed with HIV-1 Gag precursor. However, the released virions are not processed appropriately and show a greatly reduced viral infectivity. This suggests that the p6* is indispensable during the process of PR-mediated virus particle maturation.

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2006-07-01
2024-04-16
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References

  1. Arrigo S. J., Huffman K. 1995; Potent inhibition of human immunodeficiency virus type 1 (HIV-1) replication by inducible expression of HIV-1 PR multimers. J Virol 69:5988–5994
    [Google Scholar]
  2. Bleiber G., Peters S., Martinez R., Cmarko D., Meylan P., Telenti A. 2004; The central region of human immunodeficiency virus type 1 p6 protein (Gag residues S14–I31) is dispensable for the virus in vitro . J Gen Virol 85:921–927 [CrossRef]
    [Google Scholar]
  3. Burstein H., Bizub D., Skalka A. M. 1991; Assembly and processing of avian retroviral gag polyproteins containing linked protease dimers. J Virol 65:6165–6172
    [Google Scholar]
  4. Chen Y.-L., Ts'ai P.-W., Yang C.-C., Wang C.-T. 1997; Generation of infectious virus particles by transient co-expression of human immunodeficiency virus type 1 gag mutants. J Gen Virol 78:2497–2501
    [Google Scholar]
  5. Chen S.-W., Chiu H.-C., Liao W.-H., Wang F. D., Chen S.-S., Wang C.-T. 2004; The virus-associated human immunodeficiency virus type 1 Gag-Pol carrying an active protease domain in the matrix region is severely defective both in autoprocessing and in trans processing of gag particles. Virology 318:534–541 [CrossRef]
    [Google Scholar]
  6. Chiu H.-C., Yao S.-Y., Wang C.-T. 2002; Coding sequences upstream of the human immunodeficiency virus type 1 reverse transcriptase domain in Gag-Pol are not essential for incorporation of the Pr160 gag-pol into virus particles. J Virol 76:3221–3231 [CrossRef]
    [Google Scholar]
  7. Engelman A., Englund G., Orenstein J. M., Martin M. A., Craigie R. 1995; Multiple effects of mutations in human immunodeficiency virus type 1 integrase on viral replication. J Virol 69:2729–2736
    [Google Scholar]
  8. Erickson-Viitanen S., Manfredi J., Viitanen P., Tribe D. E., Tritch R., Hutchison C. A. III, Loeb D. D., Swanstrom R. 1989; Cleavage of HIV-1 gag polyprotein synthesized in vitro: sequential cleavage by the viral protease. AIDS Res Hum Retroviruses 5:577–591 [CrossRef]
    [Google Scholar]
  9. Freed E. O. 1998; HIV Gag proteins: diverse functions in the virus life cycle. Virology 251:1–15 [CrossRef]
    [Google Scholar]
  10. Gottlinger H. G., Sodroski J. G., Haseltine W. A. 1989; Role of capsid precursor processing and myristoylation in morphogenesis and infectivity of human immunodeficiency virus 1. Proc Natl Acad Sci U S A 86:5781–5785 [CrossRef]
    [Google Scholar]
  11. Henderson L. E., Bowers M. A., Sowder R. C. II, Serabyn S. A., Johnson D. G., Bess J. W. Jr, Arthur L. O., Bryant D. K., Fenselau C. 1992; Gag proteins of the highly replicative MN strain of human immunodeficiency virus type 1: posttranslational modifications, proteolytic processing, and complete amino acid sequences. J Virol 66:1856–1865
    [Google Scholar]
  12. Hunter E. 1994; Macromolecular interactions in the assembly of HIV and other retroviruses. Semin Virol 5:71–83 [CrossRef]
    [Google Scholar]
  13. Jacks T., Power M. D., Masiarz F. R., Luciw P. A., Barr P. J., Varmus H. E. 1988; Characterization of ribosomal frameshifting in HIV-1 gag-pol expression. Nature 331:280–283 [CrossRef]
    [Google Scholar]
  14. Kaplan A. H., Manchester M., Swanstorm M. 1994; The activity of the protease of human immunodeficiency virus type 1 is initiated at the membrane of infected cells before the release of viral proteins and is required for release to occur with maximum efficiency. J Virol 68:6782–6786
    [Google Scholar]
  15. Kohl N. E., Emini E. A., Schleif W. E., Davis L. J., Heimbach J. C., Dixon R. A. F., Scolnick E. M., Sigal I. S. 1988; Active human immunodeficiency virus protease is required for viral infectivity. Proc Natl Acad Sci U S A 85:4686–4890 [CrossRef]
    [Google Scholar]
  16. Krausslich H.-G. 1991; Human immunodeficiency virus proteinase dimer as component of the viral polyprotein prevents particle assembly and viral infectivity. Proc Natl Acad Sci U S A 883213–3217 [CrossRef]
    [Google Scholar]
  17. Leis J., Baltimore D., Bishop J. B. & 8 other authors 1988; Standardized and simplified nomenclature for proteins common to all retroviruses. J Virol 62:1808–1809
    [Google Scholar]
  18. Liao W.-H., Wang C.-T. 2004; Characterization of human immunodeficiency virus type 1 Pr160 gag-pol mutants with truncations downstream of the protease domain. Virology 329:180–188 [CrossRef]
    [Google Scholar]
  19. Louis J. M., Dyda F., Nashed N. T., Kimmel A. R., Davies D. R. 1998; Hydrophilic peptides derived from the transframe region of Gag-Pol inhibit the HIV-1 protease. Biochemistry 37:2105–2110 [CrossRef]
    [Google Scholar]
  20. Louis J. M., Clore G. M., Gronenborn A. M. 1999; Autoprocessing of HIV-1 protease is tightly coupled to protein folding. Nat Struct Biol 6:868–875 [CrossRef]
    [Google Scholar]
  21. Mak J., Jiang M., Wainberg M. A., Hammarskjöld M. L., Rekosh D., Kleiman L. 1994; Role of Pr160gag-pol in mediating the selective incorporation of tRNA(Lys) into human immunodeficiency virus type 1 particles. J Virol 68:2065–2072
    [Google Scholar]
  22. Mervis R. J., Ahmad N., Lillehoj E. P., Raum M. G., Salazar F. H. R., Chan H. W., Venkatesan V. 1988; The gag gene products of human immunodeficiency virus type 1: alignment within the gag open reading frame, identification of posttranslational modifications, and evidence for alternative gag precursors. J Virol 62:3993–4002
    [Google Scholar]
  23. Navia M. A., McKeever B. M. 1990; A role for the aspartyl protease from the human immunodeficiency type 1 (HIV-1) in the orchestration of virus assembly. Ann N Y Acad Sci 616:73–85 [CrossRef]
    [Google Scholar]
  24. Page K. A., Landau N. R., Littman D. R. 1990; Construction and use of a human immunodeficiency virus vector for analysis of virus infectivity. J Virol 64:5270–5276
    [Google Scholar]
  25. Park J., Morrow C. D. 1991; Overexpression of the gag-pol precursor from human immunodeficiency virus type 1 proviral genomes results in efficient proteolytic processing in the absence of virion production. J Virol 65:5111–5117
    [Google Scholar]
  26. Partin K., Krausslich H. G., Ehrlich L., Wimmer E., Carter C. 1990; Mutational analysis of a native substrate of the human immunodeficiency virus type 1 proteinase. J Virol 64:3938–3947
    [Google Scholar]
  27. Partin K., Zybarth G., Ehrlich L., DeCrombrugghe M., Wimmer E., Carter C. 1991; Deletion of sequences upstream of the proteinase improves the proteolytic processing of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A 88:4776–4780 [CrossRef]
    [Google Scholar]
  28. Paulus C., Hellebrand S., Tessmer U., Wolf H., Krausslich H.-G., Wagner R. 1999; Competitive inhibition of immunodeficiency virus type 1 protease by the Gag-Pol transframe protein. J Biol Chem 274:21539–21543 [CrossRef]
    [Google Scholar]
  29. Paulus C., Ludwig C., Wagner R. 2004; Contribution of the Gag-Pol transframe domain p6* and its coding sequence to morphogenesis and replication of human immunodeficiency virus type 1. Virology 330:271–283 [CrossRef]
    [Google Scholar]
  30. Peng C., Ho B. K., Chang T. W., Chang N. T. 1989; Role of human immunodeficiency virus type 1-specific protease in core protein maturation and viral infectivity. J Virol 63:2550–2556
    [Google Scholar]
  31. Pettit S. C., Gulnik S., Everitt L., Kaplan A. H. 2003; The dimer interfaces of protease and extra-protease domains influence the activation of protease and the stability of Gag-Pol cleavage. J Virol 77:366–374 [CrossRef]
    [Google Scholar]
  32. Quillent C., Borman A. M., Paulous S., Dauguet C., Clavel F. 1996; Extensive regions of pol are required for efficient human immunodeficiency virus polyprotein processing and particle maturation. Virology 219:29–36 [CrossRef]
    [Google Scholar]
  33. Rose J. R., Babe L. M., Craik C. S. 1995; Defining the level of human immunodeficiency virus type 1 (HIV-1) protease activity required for HIV-1 particle maturation and infectivity. J Virol 69:2751–2758
    [Google Scholar]
  34. Sambrook J., Russell D. W. 2001 Molecular Cloning: a Laboratory Manual , 3rd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  35. Shehu-Xhilaga M., Crowe S. M., Mak J. 2001; Maintenance of the Gag/Gag-Pol ratio is important for human immunodeficiency virus type 1 RNA dimerization and viral infectivity. J Virol 75:1834–1841 [CrossRef]
    [Google Scholar]
  36. Swanstrom R., Wills J. W. 1997; Synthesis, assembly, and processing of viral proteins. In Retroviruses Edited by Coffin J. M., Hughes S. H., Varmus H. E. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  37. Tessmer U., Krausslich H.-G. 1998; Cleavage of human immunodeficiency virus type 1 proteinase from the N-terminally adjacent p6* protein is essential for efficient Gag polyprotein processing and viral infectivity. J Virol 72:3459–3463
    [Google Scholar]
  38. Wang C.-T., Lai H.-Y., Li J.-J. 1998; Analysis of minimal human immunodeficiency virus type 1 gag coding sequences capable of virus-like particle assembly and release. J Virol 72:7950–7959
    [Google Scholar]
  39. Wang C.-T., Chou Y.-C., Chiang C.-C. 2000; Assembly and processing of human immunodeficiency virus gag mutants containing a partial replacement of the matrix domain by the viral protease domain. J Virol 74:3418–3422 [CrossRef]
    [Google Scholar]
  40. Wills J. W., Craven R. C. 1991; Form, function, and use of retroviral gag proteins. AIDS 5:639–654 [CrossRef]
    [Google Scholar]
  41. Wondrak E. M., Louis J. M. 1996; Influence of flanking sequences on the dimer stability of human immunodeficiency virus type 1 protease. Biochemistry 35:12957–12962 [CrossRef]
    [Google Scholar]
  42. Xiang Y., Ridky T. W., Krishna N. K., Leis J. 1997; Altered Rous sarcoma virus Gag polyprotein processing and its effects on particle formation. J Virol 71:2083–2091
    [Google Scholar]
  43. Yee J. K., Friedmann T., Burns J. C. 1994; Generation of high-titer pseudotyped retroviral vectors with very broad host range. Methods Cell Biol 43:99–112
    [Google Scholar]
  44. Zybarth G., Carter C. 1995; Domains upstream of the protease (PR) in human immunodeficiency virus type 1 Gag-Pol influence PR autoprocessing. J Virol 69:3878–3884
    [Google Scholar]
  45. Zybarth G., Krausslich H. G., Partin K., Carter C. 1994; Proteolytic activity of novel human immunodeficiency virus type 1 proteinase proteins from a precursor with a blocking mutation at the N terminus of the PR domain. J Virol 68:240–250
    [Google Scholar]
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