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 Apr 15;90(8):3544–3548. doi: 10.1073/pnas.90.8.3544

A virion-specific inhibitory molecule with therapeutic potential for human immunodeficiency virus type 1.

Z Matsuda 1, X Yu 1, Q C Yu 1, T H Lee 1, M Essex 1
PMCID: PMC46337  PMID: 7682710

Abstract

A potential new approach for gene therapy against human immunodeficiency virus type 1 (HIV-1) infection is the design of a nonstructural gene-based virion-specific inhibitory molecule that is packaged with virus to destroy its infectivity. We tested this approach for HIV-1 by using Vpx, a virion-associated protein of HIV-2 and simian immunodeficiency virus. Vpx was incorporated into HIV-1 virions and the resulting cell-free virus lost infectivity in CD4+ human T cells. This demonstrates the therapeutic potential of an accessory gene-based virion-specific inhibitory molecule. Vpx and its derivatives can be regarded as a new class of anti-HIV-1 molecule.

Full text

PDF
3544

Images in this article

3546Fig. 3
on p.3546

Selected References

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

  1. Cohen E. A., Dehni G., Sodroski J. G., Haseltine W. A. Human immunodeficiency virus vpr product is a virion-associated regulatory protein. J Virol. 1990 Jun;64(6):3097–3099. doi: 10.1128/jvi.64.6.3097-3099.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Franchini G., Rusche J. R., O'Keeffe T. J., Wong-Staal F. The human immunodeficiency virus type 2 (HIV-2) contains a novel gene encoding a 16 kD protein associated with mature virions. AIDS Res Hum Retroviruses. 1988 Aug;4(4):243–250. doi: 10.1089/aid.1988.4.243. [DOI] [PubMed] [Google Scholar]
  3. Freed E. O., Delwart E. L., Buchschacher G. L., Jr, Panganiban A. T. A mutation in the human immunodeficiency virus type 1 transmembrane glycoprotein gp41 dominantly interferes with fusion and infectivity. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):70–74. doi: 10.1073/pnas.89.1.70. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Green M., Ishino M., Loewenstein P. M. Mutational analysis of HIV-1 Tat minimal domain peptides: identification of trans-dominant mutants that suppress HIV-LTR-driven gene expression. Cell. 1989 Jul 14;58(1):215–223. doi: 10.1016/0092-8674(89)90417-0. [DOI] [PubMed] [Google Scholar]
  5. 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. doi: 10.1002/j.1460-2075.1989.tb03488.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Henderson L. E., Sowder R. C., Copeland T. D., Benveniste R. E., Oroszlan S. Isolation and characterization of a novel protein (X-ORF product) from SIV and HIV-2. Science. 1988 Jul 8;241(4862):199–201. doi: 10.1126/science.3388031. [DOI] [PubMed] [Google Scholar]
  7. 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. doi: 10.1016/0042-6822(89)90574-6. [DOI] [PubMed] [Google Scholar]
  8. Kappes J. C., Conway J. A., Lee S. W., Shaw G. M., Hahn B. H. Human immunodeficiency virus type 2 vpx protein augments viral infectivity. Virology. 1991 Sep;184(1):197–209. doi: 10.1016/0042-6822(91)90836-z. [DOI] [PubMed] [Google Scholar]
  9. Kappes J. C., Morrow C. D., Lee S. W., Jameson B. A., Kent S. B., Hood L. E., Shaw G. M., Hahn B. H. Identification of a novel retroviral gene unique to human immunodeficiency virus type 2 and simian immunodeficiency virus SIVMAC. J Virol. 1988 Sep;62(9):3501–3505. doi: 10.1128/jvi.62.9.3501-3505.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kornfeld H., Riedel N., Viglianti G. A., Hirsch V., Mullins J. I. Cloning of HTLV-4 and its relation to simian and human immunodeficiency viruses. Nature. 1987 Apr 9;326(6113):610–613. doi: 10.1038/326610a0. [DOI] [PubMed] [Google Scholar]
  11. Kunkel T. A. Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc Natl Acad Sci U S A. 1985 Jan;82(2):488–492. doi: 10.1073/pnas.82.2.488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Malim M. H., Böhnlein S., Hauber J., Cullen B. R. Functional dissection of the HIV-1 Rev trans-activator--derivation of a trans-dominant repressor of Rev function. Cell. 1989 Jul 14;58(1):205–214. doi: 10.1016/0092-8674(89)90416-9. [DOI] [PubMed] [Google Scholar]
  13. Marcon L., Michaels F., Hattori N., Fargnoli K., Gallo R. C., Franchini G. Dispensable role of the human immunodeficiency virus type 2 Vpx protein in viral replication. J Virol. 1991 Jul;65(7):3938–3942. doi: 10.1128/jvi.65.7.3938-3942.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Natsoulis G., Boeke J. D. New antiviral strategy using capsid-nuclease fusion proteins. Nature. 1991 Aug 15;352(6336):632–635. doi: 10.1038/352632a0. [DOI] [PubMed] [Google Scholar]
  15. Ogawa K., Shibata R., Kiyomasu T., Higuchi I., Kishida Y., Ishimoto A., Adachi A. Mutational analysis of the human immunodeficiency virus vpr open reading frame. J Virol. 1989 Sep;63(9):4110–4114. doi: 10.1128/jvi.63.9.4110-4114.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ratner L., Fisher A., Jagodzinski L. L., Mitsuya H., Liou R. S., Gallo R. C., Wong-Staal F. Complete nucleotide sequences of functional clones of the AIDS virus. AIDS Res Hum Retroviruses. 1987 Spring;3(1):57–69. doi: 10.1089/aid.1987.3.57. [DOI] [PubMed] [Google Scholar]
  17. 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. doi: 10.1002/j.1460-2075.1992.tb05419.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Tristem M., Marshall C., Karpas A., Petrik J., Hill F. Origin of vpx in lentiviruses. Nature. 1990 Sep 27;347(6291):341–342. doi: 10.1038/347341b0. [DOI] [PubMed] [Google Scholar]
  19. Trono D., Feinberg M. B., Baltimore D. HIV-1 Gag mutants can dominantly interfere with the replication of the wild-type virus. Cell. 1989 Oct 6;59(1):113–120. doi: 10.1016/0092-8674(89)90874-x. [DOI] [PubMed] [Google Scholar]
  20. Yu X. F., Ito S., Essex M., Lee T. H. A naturally immunogenic virion-associated protein specific for HIV-2 and SIV. Nature. 1988 Sep 15;335(6187):262–265. doi: 10.1038/335262a0. [DOI] [PubMed] [Google Scholar]
  21. Yu X. F., Yu Q. C., Essex M., Lee T. H. The vpx gene of simian immunodeficiency virus facilitates efficient viral replication in fresh lymphocytes and macrophage. J Virol. 1991 Sep;65(9):5088–5091. doi: 10.1128/jvi.65.9.5088-5091.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Yuan X., Matsuda Z., Matsuda M., Essex M., Lee T. H. Human immunodeficiency virus vpr gene encodes a virion-associated protein. AIDS Res Hum Retroviruses. 1990 Nov;6(11):1265–1271. doi: 10.1089/aid.1990.6.1265. [DOI] [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