Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Aug 1;90(15):7381–7385. doi: 10.1073/pnas.90.15.7381

Vpu protein of human immunodeficiency virus type 1 enhances the release of capsids produced by gag gene constructs of widely divergent retroviruses.

H G Göttlinger 1, T Dorfman 1, E A Cohen 1, W A Haseltine 1
PMCID: PMC47141  PMID: 8346259

Abstract

The Vpu protein of human immunodeficiency virus type 1 facilitates the release of virus particles from the surface of infected cells. The ability of the Vpu protein to facilitate release of Gag proteins from retroviruses that lack a Vpu-like protein was examined. The results of these experiments show that Vpu significantly increases the release of the Gag proteins of human immunodeficiency virus type 2, visna virus, and Moloney murine leukemia virus from HeLa cells. The results indicate that Vpu-mediated enhancement of particle release requires neither amino-terminal myristoylation of the Gag precursor nor cleavage of the Gag precursor by the viral protease. The results raise the possibility that Vpu modifies a cellular pathway common to the release of all retroviruses from the cell surface.

Full text

PDF
7381

Images in this article

7382Fig. 2
on p.7382
7383Fig. 3
on p.7383
7383Fig. 4
on p.7383
7384Fig. 5
on p.7384

Selected References

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

  1. Adachi A., Gendelman H. E., Koenig S., Folks T., Willey R., Rabson A., Martin M. A. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J Virol. 1986 Aug;59(2):284–291. doi: 10.1128/jvi.59.2.284-291.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brun-Vezinet F., Rey M. A., Katlama C., Girard P. M., Roulot D., Yeni P., Lenoble L., Clavel F., Alizon M., Gadelle S. Lymphadenopathy-associated virus type 2 in AIDS and AIDS-related complex. Clinical and virological features in four patients. Lancet. 1987 Jan 17;1(8525):128–132. doi: 10.1016/s0140-6736(87)91967-2. [DOI] [PubMed] [Google Scholar]
  3. Bryant M., Ratner L. Myristoylation-dependent replication and assembly of human immunodeficiency virus 1. Proc Natl Acad Sci U S A. 1990 Jan;87(2):523–527. doi: 10.1073/pnas.87.2.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Clavel F., Guyader M., Guétard D., Sallé M., Montagnier L., Alizon M. Molecular cloning and polymorphism of the human immune deficiency virus type 2. Nature. 1986 Dec 18;324(6098):691–695. doi: 10.1038/324691a0. [DOI] [PubMed] [Google Scholar]
  5. Cohen E. A., Terwilliger E. F., Sodroski J. G., Haseltine W. A. Identification of a protein encoded by the vpu gene of HIV-1. Nature. 1988 Aug 11;334(6182):532–534. doi: 10.1038/334532a0. [DOI] [PubMed] [Google Scholar]
  6. Colicelli J., Goff S. P. Sequence and spacing requirements of a retrovirus integration site. J Mol Biol. 1988 Jan 5;199(1):47–59. doi: 10.1016/0022-2836(88)90378-6. [DOI] [PubMed] [Google Scholar]
  7. Cullen B. R. Use of eukaryotic expression technology in the functional analysis of cloned genes. Methods Enzymol. 1987;152:684–704. doi: 10.1016/0076-6879(87)52074-2. [DOI] [PubMed] [Google Scholar]
  8. Dayton A. I., Sodroski J. G., Rosen C. A., Goh W. C., Haseltine W. A. The trans-activator gene of the human T cell lymphotropic virus type III is required for replication. Cell. 1986 Mar 28;44(6):941–947. doi: 10.1016/0092-8674(86)90017-6. [DOI] [PubMed] [Google Scholar]
  9. Feinberg M. B., Jarrett R. F., Aldovini A., Gallo R. C., Wong-Staal F. HTLV-III expression and production involve complex regulation at the levels of splicing and translation of viral RNA. Cell. 1986 Sep 12;46(6):807–817. doi: 10.1016/0092-8674(86)90062-0. [DOI] [PubMed] [Google Scholar]
  10. Göttlinger H. G., Dorfman T., Sodroski J. G., Haseltine W. A. Effect of mutations affecting the p6 gag protein on human immunodeficiency virus particle release. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3195–3199. doi: 10.1073/pnas.88.8.3195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Göttlinger H. G., Sodroski J. G., Haseltine W. A. Role of capsid precursor processing and myristoylation in morphogenesis and infectivity of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5781–5785. doi: 10.1073/pnas.86.15.5781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hansen M., Jelinek L., Whiting S., Barklis E. Transport and assembly of gag proteins into Moloney murine leukemia virus. J Virol. 1990 Nov;64(11):5306–5316. doi: 10.1128/jvi.64.11.5306-5316.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jones T. A., Blaug G., Hansen M., Barklis E. Assembly of gag-beta-galactosidase proteins into retrovirus particles. J Virol. 1990 May;64(5):2265–2279. doi: 10.1128/jvi.64.5.2265-2279.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Klimkait T., Strebel K., Hoggan M. D., Martin M. A., Orenstein J. M. The human immunodeficiency virus type 1-specific protein vpu is required for efficient virus maturation and release. J Virol. 1990 Feb;64(2):621–629. doi: 10.1128/jvi.64.2.621-629.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. McClure M. A., Johnson M. S., Feng D. F., Doolittle R. F. Sequence comparisons of retroviral proteins: relative rates of change and general phylogeny. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2469–2473. doi: 10.1073/pnas.85.8.2469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pal R., Mumbauer S., Hoke G. M., Takatsuki A., Sarngadharan M. G. Brefeldin A inhibits the processing and secretion of envelope glycoproteins of human immunodeficiency virus type 1. AIDS Res Hum Retroviruses. 1991 Aug;7(8):707–712. doi: 10.1089/aid.1991.7.707. [DOI] [PubMed] [Google Scholar]
  17. Peng C., Ho B. K., Chang T. W., Chang N. T. Role of human immunodeficiency virus type 1-specific protease in core protein maturation and viral infectivity. J Virol. 1989 Jun;63(6):2550–2556. doi: 10.1128/jvi.63.6.2550-2556.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rein A., McClure M. R., Rice N. R., Luftig R. B., Schultz A. M. Myristylation site in Pr65gag is essential for virus particle formation by Moloney murine leukemia virus. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7246–7250. doi: 10.1073/pnas.83.19.7246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rossmann M. G., Johnson J. E. Icosahedral RNA virus structure. Annu Rev Biochem. 1989;58:533–573. doi: 10.1146/annurev.bi.58.070189.002533. [DOI] [PubMed] [Google Scholar]
  20. Schwartz S., Felber B. K., Fenyö E. M., Pavlakis G. N. Env and Vpu proteins of human immunodeficiency virus type 1 are produced from multiple bicistronic mRNAs. J Virol. 1990 Nov;64(11):5448–5456. doi: 10.1128/jvi.64.11.5448-5456.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Schätzl H., Gelderblom H. R., Nitschko H., von der Helm K. Analysis of non-infectious HIV particles produced in presence of HIV proteinase inhibitor. Arch Virol. 1991;120(1-2):71–81. doi: 10.1007/BF01310950. [DOI] [PubMed] [Google Scholar]
  22. Staskus K. A., Retzel E. F., Lewis E. D., Silsby J. L., St Cyr S., Rank J. M., Wietgrefe S. W., Haase A. T., Cook R., Fast D. Isolation of replication-competent molecular clones of visna virus. Virology. 1991 Mar;181(1):228–240. doi: 10.1016/0042-6822(91)90488-w. [DOI] [PubMed] [Google Scholar]
  23. Stephens R. M., Casey J. W., Rice N. R. Equine infectious anemia virus gag and pol genes: relatedness to visna and AIDS virus. Science. 1986 Feb 7;231(4738):589–594. doi: 10.1126/science.3003905. [DOI] [PubMed] [Google Scholar]
  24. Strebel K., Klimkait T., Martin M. A. A novel gene of HIV-1, vpu, and its 16-kilodalton product. Science. 1988 Sep 2;241(4870):1221–1223. doi: 10.1126/science.3261888. [DOI] [PubMed] [Google Scholar]
  25. Terwilliger E. F., Cohen E. A., Lu Y. C., Sodroski J. G., Haseltine W. A. Functional role of human immunodeficiency virus type 1 vpu. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5163–5167. doi: 10.1073/pnas.86.13.5163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Towler D. A., Eubanks S. R., Towery D. S., Adams S. P., Glaser L. Amino-terminal processing of proteins by N-myristoylation. Substrate specificity of N-myristoyl transferase. J Biol Chem. 1987 Jan 25;262(3):1030–1036. [PubMed] [Google Scholar]
  27. Willey R. L., Maldarelli F., Martin M. A., Strebel K. Human immunodeficiency virus type 1 Vpu protein regulates the formation of intracellular gp160-CD4 complexes. J Virol. 1992 Jan;66(1):226–234. doi: 10.1128/jvi.66.1.226-234.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Yao X. J., Göttlinger H., Haseltine W. A., Cohen E. A. Envelope glycoprotein and CD4 independence of vpu-facilitated human immunodeficiency virus type 1 capsid export. J Virol. 1992 Aug;66(8):5119–5126. doi: 10.1128/jvi.66.8.5119-5126.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES