RNA — Protein Interactions Required for Rev Mediated Regulation of HIV Gene Expression

  • Craig A. Rosen
  • Alan W. Cochrane
  • Patrick J. Dillon
  • Henrik S. Olsen
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


Regulation of HIV gene expression is controlled by the interaction of cellular and viral transacting factors with cis-acting elements dispersed within the viral DNA and RNA. As a member of the lentivirus family of retroviruses, HIV encodes several non-structural regulatory proteins in addition to the gag, pol, and env genes common to all retroviruses. Two of these proteins, referred to as Tat1,2 and Rev3,4, are essential positive regulators of gene expression. The Rev protein is a 19 kD nuclear5,6 phosphoprotein7,8 required for expression of structural gene products3,4. Regulation is achieved via a mechanism involving a productive export of nuclear entrapped structural mRNAs to the cytoplasm6,9–11. Although the precise mechanism for this process remains unknown, interaction of the Rev protein with a structured RNA target sequence (RRE)12 present in the env gene is required.


Human Immunodeficiency Virus Human Immunodeficiency Virus Type Base Pairing Interaction Primary Nucleotide Sequence Hairpin Loop Structure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    S.K. Arya, C. Guo, S.F. Josephs and F. Wong-Staal, Trans-activator gene of human T-lymphotrophic virus type III (HTLV-III), Science 229: 69 (1985).PubMedCrossRefGoogle Scholar
  2. 2.
    J. Sodroski, C.A. Rosen and W.A. Haseltine, Trans-acting transcriptional activation of the long terminal repeat of human T lymphotropic viruses in infected cells, Science 225: 381 (1984).PubMedCrossRefGoogle Scholar
  3. 3.
    J. Sodroski, W.C. Goh, C. Rosen, A. Dayton, E. Terwilliger and W.A. Haseltine, A second post-transcriptional transactivator gene required for the HTLV-III replication, Nature 321: 412 (1986).PubMedCrossRefGoogle Scholar
  4. 4.
    M.B. Feinberg, R.F. Jarrett, A. Aldovini, R.C. Gallo and F. Wong-Staal, HTLV-III expression and production involve complex regulation at the levels of splicing and translation of viral RNA, Cell 46: 807 (1986).PubMedCrossRefGoogle Scholar
  5. 5.
    B.R. Cullen, J. Hauber, K. Campbell, J.G. Sodroski, W.A. Haseltine and C.A. Rosen, Subcellular localization of the human immunodeficiency virus trans-acting art gene product, J. Virol. 62: 2498 (1988).Google Scholar
  6. 6.
    B.K. Felber, M. Hadzopoulou-Cladaras, C. Cladaras, T. Copeland and G.N. Pavlakis, The rev protein of HIV-1 affects the stability and transport of the viral mRNA, Proc. Natl. Acad. Sci. USA 86: 1495 (1989).PubMedCrossRefGoogle Scholar
  7. 7.
    J. Hauber, M. Bouvier, M.H. Malim and B.R. Cullen, Phosphorylation of the human immunodeficiency virus art/trs gene product is enhanced by activation of protein kinase C, J. Virol. 62: 4801 (1988).Google Scholar
  8. 8.
    A. Cochrane, R. Kramer, S. Ruben, J. Levine and C.A. Rosen, The human immunodeficiency virus rev protein is a nuclear phosphoprotein, Virology 171: 264 (1989).PubMedCrossRefGoogle Scholar
  9. 9.
    M. Hadzopoulou-Cladaras, B.K. Felber, C. Cladaras, A.A. Athanassopoulos, A. Tse and G.N. Pavlakis, The rev (trs/art) protein of the human immunodeficiency virus type 1 affects viral mRNA and protein expression via a cis-acting sequence in the env region, J. Virol. 63: 1265 (1989).PubMedGoogle Scholar
  10. 10.
    M.L. Hammarskjöld, J. Heijmer, B. Hammarskjöld, I. Sangwan, L. Albert and D. Rekosh, Regulation of human immunodeficiency virus env expression by the rev gene product, J. Virol. 63: 1959 (1989).Google Scholar
  11. 11.
    M. Emerman, R. Vazeux and K. Peden, The rev gene product of the human immunodeficiency virus affects envelope-specific RNA localization, Cell 57: 1155 (1989).PubMedCrossRefGoogle Scholar
  12. 12.
    M.H. Malim, J. Hauber, S.-Y. Le, J.V. Maizel and B.R. Cullen, The HIV-1 rev transactivator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA, Nature 338: 254 (1989).PubMedCrossRefGoogle Scholar
  13. 13.
    C.A. Rosen, E. Terwilliger, A. Dayton, J.G. Sodroski and W.A. Haseltine, Intragenic cis-acting art gene-responsive sequences of the human immunodeficiency virus, Proc. Natl. Acad. Sci. USA 85: 2071 (1988).PubMedCrossRefGoogle Scholar
  14. 14.
    A.W. Cochrane, C.H. Chen, R. Kramer, L. Tomchak and C.A. Rosen, Purification of biologically active human immunodeficiency virus rev protein from E. coli, Virology 173: 335 (1989).PubMedCrossRefGoogle Scholar
  15. 15.
    A.W. Cochrane, C.-H. Chen and C. Rosen, Specific interaction of the HIV Rev transactivator protein with a structured region in the env mRNA, Proc. Natl. Acad. Sci. USA 87: 1198 (1990).PubMedCrossRefGoogle Scholar
  16. 16.
    H. Olsen, P. Nelbock, A. Cochrane and C. Rosen, Secondary structure is the major determinant for interaction of HIV Rev protein with RNA, Science 247: 845 (1990).PubMedCrossRefGoogle Scholar
  17. 17.
    M.H. Malim, S. Bohnlein, R. Fenrick, S.-Y. Lee, J.V. Maizel and B.R. Cullen, Functional comparison of the Rev transactivators encoded by different primate immunodeficiency virus species, Proc. Natl. Acad. Sci. USA 86: 8222 (1989).PubMedCrossRefGoogle Scholar
  18. 18.
    M.H. Malim, L.S. Tiley, D.F. McCarn, J.R. Rusche, J. Hauber and B.R. Cullen, HIV-1 structural gene expression requires binding of the Rev transactivator to its RNA target sequence, Cell 60: 675 (1990).PubMedCrossRefGoogle Scholar
  19. 19.
    S. Heaphy, C. Dingwall, I. Ernberg, M.J. Gait, S.M. Green, J. Karn, A.D. Lowe, et al, HIV-1 regulator of virion expression (Rev) protein binds to an RNA stem-loop structure located within the Rev response element, Cell 60: 685 (1990).PubMedCrossRefGoogle Scholar
  20. 20.
    E. Dayton, D. Powell and A. Dayton, Functional analysis of CAR, the target sequence for the rev protein of HIV-1, Science 246: 1625 (1989).PubMedCrossRefGoogle Scholar
  21. 21.
    M. Emerman, M. Guyader, L. Montagnier, D. Baltimore and M. Muesing, The specificity of the human immunodeficiency virus type 2 transactivator is different from that of human immunodeficiency virus type 1, EMBO J. 6: 3755 (1987).Google Scholar
  22. 22.
    P.J. Dillon, P. Nelbock, A. Perkins and C.A. Rosen, Function of the human immunodeficiency virus types 1 and 2 Rev proteins is dependent upon their ability to interact with a structured region present in the env gene mRNA, J. Virol. (1990).(In Press)Google Scholar
  23. 23.
    L. Rimsky, J. Hauber, M. Dukovich, M.H. Malim, H. Langlois, B.R. Cullen and W.C. Greene, Functional replacement of the HIV-1 rev protein by the HTLV-1 rex protein, Nature 335: 738 (1988).PubMedCrossRefGoogle Scholar
  24. 24.
    S.M. Hanly, L.T. Rimsky, M.H. Malim, J.J. Kim, J. Hauber, M. DucDodon, S.-Y. Le, et al, Comparative analysis of the HTLV-1 rex and HIV-1 rev trans-regulatory proteins and their RNA response elements, Genes Dev 3: 1534 (1989).PubMedCrossRefGoogle Scholar
  25. 25.
    H.S. Olsen, A.W. Cochrane, P.J. Dillon, C.M. Nalin and C.A. Rosen, Interaction of the human immunodeficiency virus type 1 Rev protein with a structured region in env mRNA is dependent upon multimer formation mediated through a basic stretch of amino acids, Genes Dev (1990).Google Scholar
  26. 26.
    A.W. Cochrane, E. Golub, D. Volsky, S. Ruben and C.A. Rosen, Functional significance of phosphorylation to the human immunodeficiency virus rev protein, J. Virol. 63: 4438 (1989).PubMedGoogle Scholar
  27. 27.
    M.H. Malim, S. Bohnlein, J. Hauber and B.R. Cullen, Functional dissection of the 111V-1 rev trans-activator - derivation of a trans-dominant repressor of rev function, Ç&1158: 205 (1989).Google Scholar
  28. 28.
    A. Perkins, A.W. Cochrane, S.M. Ruben and C.A. Rosen, Structural and functional characterization of the human immunodeficiency virus rev protein, J. AIDS 2: 256 (1989).Google Scholar
  29. 29.
    A.W. Cochrane, A. Perkins and C.A. Rosen, Identification of sequences important in the nucleolar localization of human immunodeficiency virus Rev: relevance of nucleolar localization to function, J. Virol. 64: 881 (1990).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Craig A. Rosen
  • Alan W. Cochrane
    • 1
  • Patrick J. Dillon
    • 1
  • Henrik S. Olsen
    • 1
  1. 1.Department of Molecular Oncology & VirologyRoche Institute of Molecular Biology Roche Research CenterNutleyUSA

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