A 5’ Splice Site is Essential for REV and REX Regulation of HIV Envelope Protein mRNA Expression

  • Xiaobin Lu
  • Nancy Lewis
  • David Rekosh
  • Marie-Louise Hammarskjöld
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


The organization of the HIV genome is much more complex than that of most other retroviruses (for a review see (1)). This is due to the presence of several regulatory genes in addition to the structural genes gag, pol and env. This complexity is reflected by the large number of different subgenomic mRNAs found in HIV infected cells (2). A proper balance between these mRNAs has to be achieved to ensure appropriate expression of the different viral proteins.


Human Immunodeficiency Virus Human Immunodeficiency Virus Type Splice Site Subgenomic mRNAs Human Immunodeficiency Virus Envelope Protein 
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.
    Varmus, H. Retroviruses. Science. 240: 1427–1435, (1988).PubMedCrossRefGoogle Scholar
  2. 2.
    Schwartz, S., B. K. Felber, D. M. Benko, E. M. Fenyo and G. N. Pavlakis. Cloning and functional analysis of multiply spliced mRNA species of human immunodeficiency virus type 1. J Virol. 64: 2519–2529, (1990).PubMedGoogle Scholar
  3. 3.
    Hauber, J., M. Bouvier, M. H. Malim and B. R. Cullen. Phosphorylation of the rev gene product of human immunodeficiency virus type 1. J Virol. 62: 48014804, (1988).Google Scholar
  4. 4.
    Hammarskjöld, M.-L., J. Heimer, B. Hammarskjöld, I. Sangwan, L. Albert and D. Rekosh. Regulation of human immunodeficiency virus env expression by the rev gene product. J Virol. 63: 1959–1966, (1989).PubMedGoogle Scholar
  5. 5.
    Felber, B. K., M. Hadzopoulou-Cladaras, C. Cladaras, T. Copeland and G. N. Pavlakis. Rev protein of human immunodeficiency virus type 1 affects the stability and transport of the viral mRNA. Proc Natl Acad Sci U S A. 86: 14961499, (1989).Google Scholar
  6. 6.
    Malim, M. H., J. Hauber, S. V. Le, J. V. Maizel and B. R. Cullen. The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Nature. 338: 254–257, (1989).PubMedCrossRefGoogle Scholar
  7. 7.
    Emerman, M., R. Vazeux and K. Peden. The rev gene product of the human immunodeficiency virus affects envelope-specific RNA localization. Cell. 57: 1155–1165, (1989).PubMedCrossRefGoogle Scholar
  8. 8.
    Rosen, C. A., 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: 2071–2075, (1988).PubMedCrossRefGoogle Scholar
  9. 9.
    Dayton, A. I., E. F. Terwilliger, J. Potz, M. Kowalski, J. G. Sodroski and W. A. Haseltine. Cis-acting sequences responsive to the rev gene product of the human immunodeficiency virus. J. Acquired Immune Deficiency Syndromes. 1: 441–452, (1988).Google Scholar
  10. 10.
    Hadzopoulou-Cladaras, M., B. K. Felber, C. Cladaras, A. Athanassopoulos, A. Tse and G. N. Pavlakis. 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. 63: 1265–1274, (1989).PubMedGoogle Scholar
  11. 11.
    Daly, T. J., K. S. Cook, G. S. Gray, T. E. Maione and J. R. Rusche. Specific binding of HIV-1 recombinant rev protein to the rev-responsive element in vitro. Nature. 342: 816–819, (1989).PubMedCrossRefGoogle Scholar
  12. 12.
    Zapp, M. L. and M. R. Green. Sequence-specific RNA binding by the HIV-1 Rev protein. Nature. 342: 714–716, (1989).Google Scholar
  13. 13.
    Cullen, B. R. and W. C. Greene. Regulatory pathways governing HIV-1 replication. Cell. 58: 423–426, (1989).PubMedCrossRefGoogle Scholar
  14. 14.
    Chang, D. D. and P. A. Sharp. Regulation by HIV rev depends upon recognition of splice sites. Cell. 59: 789–795, (1989).PubMedCrossRefGoogle Scholar
  15. 15.
    Hidaka, M., J. Inoue, M. Yoshida and M. Seiki. Post-transcriptional regulator (rex) of HTLV-1 initiates expression of viral structural proteins but suppresses expression of regulatory proteins. Embo J. 7: 519–523, (1988).PubMedGoogle Scholar
  16. 16.
    Seiki, M., J. Inoue, M. Hidaka and M. Yoshida. Two cis-acting elements responsible for posttranscriptional trans-regulation of gene expression of human T-cell leukemia virus type I. Proc Natl Acad Sci U S A. 85: 7124–7128, (1988).PubMedCrossRefGoogle Scholar
  17. 17.
    Lewis, N., J. Williams, D. Rekosh and M.-L. Hammarskjöld. Identification of a cis-Acting element in HIV-2 that Is responsive to the HIV-1 rev and HTLV-I and II rex proteins. J. Virol. 64: 1690–1697 (1990).PubMedGoogle Scholar
  18. 18.
    Rimsky, L., J. Hauber, M. Dukovich, M. H. Malim, A. Langlois, B. R. Cullen and W. C. Greene. Functional replacement of the HIV-1 rev protein by the HTLV-1 rex protein. Nature. 335: 738–740, (1988).PubMedCrossRefGoogle Scholar
  19. 19.
    Ahmed, Y. F., S. M. Hanly, M. H. Malim, B. R. Cullen and W. C. Greene. Structure-function analyses of the HTLV-I rex and HIV-1 rev RNA response elements: insights into the mechanism of rex and rev action. Genes Dev. 4: 1014–1022, (1990).PubMedCrossRefGoogle Scholar
  20. 20.
    Hanly, S. M., L. T. Rimsky, M. H. Malim, J. H. Kim, J. Hauber, D. M. Duc, S. Y. Le, J. V. Maizel, B. R. Cullen and W. C. Greene. Comparative analysis of the HTLV-I rex and HIV-1 rev trans-regulatory proteins and their RNA response elements. Genes Dev. 3: 1534–1544, (1989).PubMedCrossRefGoogle Scholar
  21. 21.
    Felber, B.K., D. Derse, A Athanassopoulos, M. Campbell and G.N. Pavalakis. Cross-activation of the rex proteins of HTLV-I and BLV and of the rev protein of HIV-1 and nonreciprocal interactions with their RNA Responsive Elements. New Biologist 1: 318–330Google Scholar
  22. 22.
    Smith, A. J., M. I. Cho, M. L. Hammarskjöld and D. Rekosh. Human immunodeficiency virus type 1 Pr55gag and Pr160gag-pol expressed from a simian virus 40 late replacement vector are efficiently processed and assembled into viruslike particles. J Virol. 64: 2743–2750, (1990).PubMedGoogle Scholar
  23. 23.
    Lu, X., J. Heimer, D. Rekosh and M.-L. Hammarskjöld. Ul snRNA plays a direct role in the formation of a rev regulated HIV env mRNA that Remains Unspliced. Proc Natl Acad Sci U S A. 87: 7598–7602 (1990).PubMedCrossRefGoogle Scholar
  24. 24.
    Rekosh, D., A. Nygren, P. Flodby, M. L. Hammarskjöld and H. Wigzell. Coexpression of human immunodeficiency virus envelope proteins and tat from a single simian virus 40 late replacement vector.. Proc Natl Acad Sci U S A. 85: 334–338, (1988).PubMedCrossRefGoogle Scholar
  25. 25.
    Zhuang, Y. and A. M. Weiner. A compensatory base change in U1 snRNA suppresses a 5’ splice site mutation. Cell. 46: 827–835, (1986).PubMedCrossRefGoogle Scholar
  26. 26.
    Siliciano, P. G. and C. Guthrie. 5’ splice site selection in yeast: genetic alterations in base-pairing with U1 reveal additional requirements. Genes Dev. 2: 1258–1267, (1988).PubMedCrossRefGoogle Scholar
  27. 27.
    Seraphin, B., L. Kretzner and M. Rosbash. A Ul snRNA:pre-mRNA base pairing interaction is required early in yeast spliceosome assembly but does not uniquely define the 5’ cleavage site. Embo J. 7: 2533–2538, (1988).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Xiaobin Lu
    • 1
  • Nancy Lewis
    • 1
  • David Rekosh
    • 1
  • Marie-Louise Hammarskjöld
    • 1
  1. 1.Departments of Microbiology, Biochemistry, Biological Sciences and Oral BiologyState University of New York at BuffaloBuffaloUSA

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