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
. 1990 Feb;87(3):1198–1202. doi: 10.1073/pnas.87.3.1198

Specific interaction of the human immunodeficiency virus Rev protein with a structured region in the env mRNA.

A W Cochrane 1, C H Chen 1, C A Rosen 1
PMCID: PMC53438  PMID: 2405396

Abstract

A region of potential complex secondary structure within the human immunodeficiency virus env mRNA has been implicated in Rev-mediated export of viral structural mRNAs from the nucleus to the cytoplasm. By using an RNase protection gel-mobility-shift assay, we demonstrate that purified Rev protein forms a stable complex with this Rev-responsive RNA. RNAs with mutations designed to disrupt formation of a predicted stem structure no longer interact with Rev. However, Rev binding is restored upon annealing of the two complementary RNAs that make up the stem. These results suggest that direct interaction of Rev with the Rev-responsive element could facilitate transport of human immunodeficiency virus structural mRNAs from the nucleus to the cytoplasm.

Full text

PDF
1201

Images in this article

1199Image
on p.1199
1199Image
on p.1199
1199Image
on p.1199
1200Image
on p.1200
1200Image
on p.1200

Selected References

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

  1. Arya S. K., Guo C., Josephs S. F., Wong-Staal F. Trans-activator gene of human T-lymphotropic virus type III (HTLV-III). Science. 1985 Jul 5;229(4708):69–73. doi: 10.1126/science.2990040. [DOI] [PubMed] [Google Scholar]
  2. Cochrane A. W., Chen C. H., Kramer R., Tomchak L., Rosen C. A. Purification of biologically active human immunodeficiency virus rev protein from Escherichia coli. Virology. 1989 Nov;173(1):335–337. doi: 10.1016/0042-6822(89)90252-3. [DOI] [PubMed] [Google Scholar]
  3. Cochrane A., Kramer R., Ruben S., Levine J., Rosen C. A. The human immunodeficiency virus rev protein is a nuclear phosphoprotein. Virology. 1989 Jul;171(1):264–266. doi: 10.1016/0042-6822(89)90535-7. [DOI] [PubMed] [Google Scholar]
  4. Colombini S., Arya S. K., Reitz M. S., Jagodzinski L., Beaver B., Wong-Staal F. Structure of simian immunodeficiency virus regulatory genes. Proc Natl Acad Sci U S A. 1989 Jul;86(13):4813–4817. doi: 10.1073/pnas.86.13.4813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cullen B. R., Hauber J., Campbell K., Sodroski J. G., Haseltine W. A., Rosen C. A. Subcellular localization of the human immunodeficiency virus trans-acting art gene product. J Virol. 1988 Jul;62(7):2498–2501. doi: 10.1128/jvi.62.7.2498-2501.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Dayton A. I., Terwilliger E. F., Potz J., Kowalski M., Sodroski J. G., Haseltine W. A. Cis-acting sequences responsive to the rev gene product of the human immunodeficiency virus. J Acquir Immune Defic Syndr. 1988;1(5):441–452. [PubMed] [Google Scholar]
  8. Dingwall C., Ernberg I., Gait M. J., Green S. M., Heaphy S., Karn J., Lowe A. D., Singh M., Skinner M. A., Valerio R. Human immunodeficiency virus 1 tat protein binds trans-activation-responsive region (TAR) RNA in vitro. Proc Natl Acad Sci U S A. 1989 Sep;86(18):6925–6929. doi: 10.1073/pnas.86.18.6925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Emerman M., Vazeux R., Peden K. The rev gene product of the human immunodeficiency virus affects envelope-specific RNA localization. Cell. 1989 Jun 30;57(7):1155–1165. doi: 10.1016/0092-8674(89)90053-6. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Felber B. K., Hadzopoulou-Cladaras M., Cladaras C., Copeland T., Pavlakis G. N. rev protein of human immunodeficiency virus type 1 affects the stability and transport of the viral mRNA. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1495–1499. doi: 10.1073/pnas.86.5.1495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fisher A. G., Feinberg M. B., Josephs S. F., Harper M. E., Marselle L. M., Reyes G., Gonda M. A., Aldovini A., Debouk C., Gallo R. C. The trans-activator gene of HTLV-III is essential for virus replication. 1986 Mar 27-Apr 2Nature. 320(6060):367–371. doi: 10.1038/320367a0. [DOI] [PubMed] [Google Scholar]
  13. Hadzopoulou-Cladaras M., Felber B. K., Cladaras C., Athanassopoulos A., Tse A., Pavlakis G. N. The rev (trs/art) protein of human immunodeficiency virus type 1 affects viral mRNA and protein expression via a cis-acting sequence in the env region. J Virol. 1989 Mar;63(3):1265–1274. doi: 10.1128/jvi.63.3.1265-1274.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hammarskjöld M. L., Heimer J., Hammarskjöld B., Sangwan I., Albert L., Rekosh D. Regulation of human immunodeficiency virus env expression by the rev gene product. J Virol. 1989 May;63(5):1959–1966. doi: 10.1128/jvi.63.5.1959-1966.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hauber J., Bouvier M., Malim M. H., Cullen B. R. Phosphorylation of the rev gene product of human immunodeficiency virus type 1. J Virol. 1988 Dec;62(12):4801–4804. doi: 10.1128/jvi.62.12.4801-4804.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hidaka M., Inoue J., Yoshida M., Seiki M. Post-transcriptional regulator (rex) of HTLV-1 initiates expression of viral structural proteins but suppresses expression of regulatory proteins. EMBO J. 1988 Feb;7(2):519–523. doi: 10.1002/j.1460-2075.1988.tb02840.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Knight D. M., Flomerfelt F. A., Ghrayeb J. Expression of the art/trs protein of HIV and study of its role in viral envelope synthesis. Science. 1987 May 15;236(4803):837–840. doi: 10.1126/science.3033827. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Malim M. H., Böhnlein S., Fenrick R., Le S. Y., Maizel J. V., Cullen B. R. Functional comparison of the Rev trans-activators encoded by different primate immunodeficiency virus species. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8222–8226. doi: 10.1073/pnas.86.21.8222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Malim M. H., Hauber J., Le S. Y., Maizel J. V., Cullen B. R. The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Nature. 1989 Mar 16;338(6212):254–257. doi: 10.1038/338254a0. [DOI] [PubMed] [Google Scholar]
  22. Muesing M. A., Smith D. H., Capon D. J. Regulation of mRNA accumulation by a human immunodeficiency virus trans-activator protein. Cell. 1987 Feb 27;48(4):691–701. doi: 10.1016/0092-8674(87)90247-9. [DOI] [PubMed] [Google Scholar]
  23. Perkins A., Cochrane A. W., Ruben S. M., Rosen C. A. Structural and functional characterization of the human immunodeficiency virus rev protein. J Acquir Immune Defic Syndr. 1989;2(3):256–263. [PubMed] [Google Scholar]
  24. Ratner L., Haseltine W., Patarca R., Livak K. J., Starcich B., Josephs S. F., Doran E. R., Rafalski J. A., Whitehorn E. A., Baumeister K. Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature. 1985 Jan 24;313(6000):277–284. doi: 10.1038/313277a0. [DOI] [PubMed] [Google Scholar]
  25. Rimsky L., Hauber J., Dukovich M., Malim M. H., Langlois A., Cullen B. R., Greene W. C. Functional replacement of the HIV-1 rev protein by the HTLV-1 rex protein. Nature. 1988 Oct 20;335(6192):738–740. doi: 10.1038/335738a0. [DOI] [PubMed] [Google Scholar]
  26. Rosen C. A., Sodroski J. G., Haseltine W. A. The location of cis-acting regulatory sequences in the human T cell lymphotropic virus type III (HTLV-III/LAV) long terminal repeat. Cell. 1985 Jul;41(3):813–823. doi: 10.1016/s0092-8674(85)80062-3. [DOI] [PubMed] [Google Scholar]
  27. Rosen C. A., Terwilliger E., Dayton A., Sodroski J. G., Haseltine W. A. Intragenic cis-acting art gene-responsive sequences of the human immunodeficiency virus. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2071–2075. doi: 10.1073/pnas.85.7.2071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sodroski J., Goh W. C., Rosen C., Dayton A., Terwilliger E., Haseltine W. A second post-transcriptional trans-activator gene required for HTLV-III replication. Nature. 1986 May 22;321(6068):412–417. doi: 10.1038/321412a0. [DOI] [PubMed] [Google Scholar]
  29. Sodroski J., Patarca R., Rosen C., Wong-Staal F., Haseltine W. Location of the trans-activating region on the genome of human T-cell lymphotropic virus type III. Science. 1985 Jul 5;229(4708):74–77. doi: 10.1126/science.2990041. [DOI] [PubMed] [Google Scholar]
  30. Terwilliger E., Burghoff R., Sia R., Sodroski J., Haseltine W., Rosen C. The art gene product of human immunodeficiency virus is required for replication. J Virol. 1988 Feb;62(2):655–658. doi: 10.1128/jvi.62.2.655-658.1988. [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