Characterization of human immunodeficiency virus type 1 Vif particle incorporation (original) (raw)

Abstract

The human immunodeficiency virus type 1 (HIV-1) Vif protein is necessary at the time of viral particle formation yet functionally manifests its effect after virions enter target cells. This suggests that Vif either acts on another viral protein or is itself incorporated into particles. In this study, we have examined the latter possibility. We confirm our previous observation that Vif is incorporated into human immunodeficiency virus type 1 virions at a ratio of approximately 1 molecule of Vif for every 75 to 220 molecules of p24, or 7 to 20 molecules per virion. Furthermore, we demonstrate that the relative concentration of Vif is much lower in particles than in infected cells, whereas the opposite is observed for the main virus components. The viral envelope, Nef, Vpr, Vpu, protease, reverse transcriptase, integrase, nucleocapsid, and p6gag proteins as well as the viral genomic RNA are dispensable for Vif packaging. Furthermore, mutating several highly conserved residues (H-108, C-114, C-133, L-145, and Q-146) or deleting the C-terminal 18 amino acids of Vif, either of which severely impairs Vif function, does not abolish its incorporation into virions. Finally, Vif can be packaged into murine leukemia virus particles. On the basis of these data, we conclude that the specificity of Vif incorporation into virions remains an open question.

Full Text

The Full Text of this article is available as a PDF (875.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aiken C., Trono D. Nef stimulates human immunodeficiency virus type 1 proviral DNA synthesis. J Virol. 1995 Aug;69(8):5048–5056. doi: 10.1128/jvi.69.8.5048-5056.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Akari H., Sakuragi J., Takebe Y., Tomonaga K., Kawamura M., Fukasawa M., Miura T., Shinjo T., Hayami M. Biological characterization of human immunodeficiency virus type 1 and type 2 mutants in human peripheral blood mononuclear cells. Arch Virol. 1992;123(1-2):157–167. doi: 10.1007/BF01317146. [DOI] [PubMed] [Google Scholar]
  3. Borman A. M., Quillent C., Charneau P., Dauguet C., Clavel F. Human immunodeficiency virus type 1 Vif- mutant particles from restrictive cells: role of Vif in correct particle assembly and infectivity. J Virol. 1995 Apr;69(4):2058–2067. doi: 10.1128/jvi.69.4.2058-2067.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chakrabarti L., Guyader M., Alizon M., Daniel M. D., Desrosiers R. C., Tiollais P., Sonigo P. Sequence of simian immunodeficiency virus from macaque and its relationship to other human and simian retroviruses. Nature. 1987 Aug 6;328(6130):543–547. doi: 10.1038/328543a0. [DOI] [PubMed] [Google Scholar]
  5. Danos O., Mulligan R. C. Safe and efficient generation of recombinant retroviruses with amphotropic and ecotropic host ranges. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6460–6464. doi: 10.1073/pnas.85.17.6460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fan L., Peden K. Cell-free transmission of Vif mutants of HIV-1. Virology. 1992 Sep;190(1):19–29. doi: 10.1016/0042-6822(92)91188-z. [DOI] [PubMed] [Google Scholar]
  7. Farnet C. M., Haseltine W. A. Determination of viral proteins present in the human immunodeficiency virus type 1 preintegration complex. J Virol. 1991 Apr;65(4):1910–1915. doi: 10.1128/jvi.65.4.1910-1915.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fisher A. G., Ensoli B., Ivanoff L., Chamberlain M., Petteway S., Ratner L., Gallo R. C., Wong-Staal F. The sor gene of HIV-1 is required for efficient virus transmission in vitro. Science. 1987 Aug 21;237(4817):888–893. doi: 10.1126/science.3497453. [DOI] [PubMed] [Google Scholar]
  9. Gabuzda D. H., Lawrence K., Langhoff E., Terwilliger E., Dorfman T., Haseltine W. A., Sodroski J. Role of vif in replication of human immunodeficiency virus type 1 in CD4+ T lymphocytes. J Virol. 1992 Nov;66(11):6489–6495. doi: 10.1128/jvi.66.11.6489-6495.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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. doi: 10.1016/0092-8674(95)90488-3. [DOI] [PubMed] [Google Scholar]
  11. Garrett E. D., Tiley L. S., Cullen B. R. Rev activates expression of the human immunodeficiency virus type 1 vif and vpr gene products. J Virol. 1991 Mar;65(3):1653–1657. doi: 10.1128/jvi.65.3.1653-1657.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Garvey K. J., Oberste M. S., Elser J. E., Braun M. J., Gonda M. A. Nucleotide sequence and genome organization of biologically active proviruses of the bovine immunodeficiency-like virus. Virology. 1990 Apr;175(2):391–409. doi: 10.1016/0042-6822(90)90424-p. [DOI] [PubMed] [Google Scholar]
  13. Goncalves J., Jallepalli P., Gabuzda D. H. Subcellular localization of the Vif protein of human immunodeficiency virus type 1. J Virol. 1994 Feb;68(2):704–712. doi: 10.1128/jvi.68.2.704-712.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goncalves J., Shi B., Yang X., Gabuzda D. Biological activity of human immunodeficiency virus type 1 Vif requires membrane targeting by C-terminal basic domains. J Virol. 1995 Nov;69(11):7196–7204. doi: 10.1128/jvi.69.11.7196-7204.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Guyader M., Emerman M., Sonigo P., Clavel F., Montagnier L., Alizon M. Genome organization and transactivation of the human immunodeficiency virus type 2. Nature. 1987 Apr 16;326(6114):662–669. doi: 10.1038/326662a0. [DOI] [PubMed] [Google Scholar]
  16. Hartman S. C., Mulligan R. C. Two dominant-acting selectable markers for gene transfer studies in mammalian cells. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8047–8051. doi: 10.1073/pnas.85.21.8047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Höglund S., Ohagen A., Lawrence K., Gabuzda D. Role of vif during packing of the core of HIV-1. Virology. 1994 Jun;201(2):349–355. doi: 10.1006/viro.1994.1300. [DOI] [PubMed] [Google Scholar]
  18. Karczewski M. K., Strebel K. Cytoskeleton association and virion incorporation of the human immunodeficiency virus type 1 Vif protein. J Virol. 1996 Jan;70(1):494–507. doi: 10.1128/jvi.70.1.494-507.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lever A., Gottlinger H., Haseltine W., Sodroski J. Identification of a sequence required for efficient packaging of human immunodeficiency virus type 1 RNA into virions. J Virol. 1989 Sep;63(9):4085–4087. doi: 10.1128/jvi.63.9.4085-4087.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Liu H., Wu X., Newman M., Shaw G. M., Hahn B. H., Kappes J. C. The Vif protein of human and simian immunodeficiency viruses is packaged into virions and associates with viral core structures. J Virol. 1995 Dec;69(12):7630–7638. doi: 10.1128/jvi.69.12.7630-7638.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lori F., Hall L., Lusso P., Popovic M., Markham P., Franchini G., Reitz M. S., Jr Effect of reciprocal complementation of two defective human immunodeficiency virus type 1 (HIV-1) molecular clones on HIV-1 cell tropism and virulence. J Virol. 1992 Sep;66(9):5553–5560. doi: 10.1128/jvi.66.9.5553-5560.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Michaels F. H., Hattori N., Gallo R. C., Franchini G. The human immunodeficiency virus type 1 (HIV-1) vif protein is located in the cytoplasm of infected cells and its effect on viral replication is equivalent in HIV-2. AIDS Res Hum Retroviruses. 1993 Oct;9(10):1025–1030. doi: 10.1089/aid.1993.9.1025. [DOI] [PubMed] [Google Scholar]
  23. Moore J. P., McKeating J. A., Norton W. A., Sattentau Q. J. Direct measurement of soluble CD4 binding to human immunodeficiency virus type 1 virions: gp120 dissociation and its implications for virus-cell binding and fusion reactions and their neutralization by soluble CD4. J Virol. 1991 Mar;65(3):1133–1140. doi: 10.1128/jvi.65.3.1133-1140.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Moore J. P., McKeating J. A., Weiss R. A., Sattentau Q. J. Dissociation of gp120 from HIV-1 virions induced by soluble CD4. Science. 1990 Nov 23;250(4984):1139–1142. doi: 10.1126/science.2251501. [DOI] [PubMed] [Google Scholar]
  25. Oberste M. S., Gonda M. A. Conservation of amino-acid sequence motifs in lentivirus Vif proteins. Virus Genes. 1992 Jan;6(1):95–102. doi: 10.1007/BF01703760. [DOI] [PubMed] [Google Scholar]
  26. Paxton W., Connor R. I., Landau N. R. 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. doi: 10.1128/jvi.67.12.7229-7237.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sakai H., Shibata R., Sakuragi J., Sakuragi S., Kawamura M., Adachi A. Cell-dependent requirement of human immunodeficiency virus type 1 Vif protein for maturation of virus particles. J Virol. 1993 Mar;67(3):1663–1666. doi: 10.1128/jvi.67.3.1663-1666.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Saltarelli M., Querat G., Konings D. A., Vigne R., Clements J. E. Nucleotide sequence and transcriptional analysis of molecular clones of CAEV which generate infectious virus. Virology. 1990 Nov;179(1):347–364. doi: 10.1016/0042-6822(90)90303-9. [DOI] [PubMed] [Google Scholar]
  29. Schwartz S., Felber B. K., Pavlakis G. N. Expression of human immunodeficiency virus type 1 vif and vpr mRNAs is Rev-dependent and regulated by splicing. Virology. 1991 Aug;183(2):677–686. doi: 10.1016/0042-6822(91)90996-o. [DOI] [PubMed] [Google Scholar]
  30. Shibata R., Kawamura M., Sakai H., Hayami M., Ishimoto A., Adachi A. Generation of a chimeric human and simian immunodeficiency virus infectious to monkey peripheral blood mononuclear cells. J Virol. 1991 Jul;65(7):3514–3520. doi: 10.1128/jvi.65.7.3514-3520.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sova P., Volsky D. J. Efficiency of viral DNA synthesis during infection of permissive and nonpermissive cells with vif-negative human immunodeficiency virus type 1. J Virol. 1993 Oct;67(10):6322–6326. doi: 10.1128/jvi.67.10.6322-6326.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Strebel K., Daugherty D., Clouse K., Cohen D., Folks T., Martin M. A. The HIV 'A' (sor) gene product is essential for virus infectivity. Nature. 1987 Aug 20;328(6132):728–730. doi: 10.1038/328728a0. [DOI] [PubMed] [Google Scholar]
  33. Talbott R. L., Sparger E. E., Lovelace K. M., Fitch W. M., Pedersen N. C., Luciw P. A., Elder J. H. Nucleotide sequence and genomic organization of feline immunodeficiency virus. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5743–5747. doi: 10.1073/pnas.86.15.5743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wain-Hobson S., Sonigo P., Danos O., Cole S., Alizon M. Nucleotide sequence of the AIDS virus, LAV. Cell. 1985 Jan;40(1):9–17. doi: 10.1016/0092-8674(85)90303-4. [DOI] [PubMed] [Google Scholar]
  35. Wieland U., Hartmann J., Suhr H., Salzberger B., Eggers H. J., Kühn J. E. In vivo genetic variability of the HIV-1 vif gene. Virology. 1994 Aug 15;203(1):43–51. doi: 10.1006/viro.1994.1453. [DOI] [PubMed] [Google Scholar]
  36. von Schwedler U., Song J., Aiken C., Trono D. Vif is crucial for human immunodeficiency virus type 1 proviral DNA synthesis in infected cells. J Virol. 1993 Aug;67(8):4945–4955. doi: 10.1128/jvi.67.8.4945-4955.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]