Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1991 Jul;65(7):3877–3881. doi: 10.1128/jvi.65.7.3877-3881.1991

Conserved functional organization of the human immunodeficiency virus type 1 and visna virus Rev proteins.

L S Tiley 1, M H Malim 1, B R Cullen 1
PMCID: PMC241419  PMID: 1645796

Abstract

Visna virus encodes a posttranscriptional regulatory protein that is functionally analogous to the Rev trans activator of human immunodeficiency virus type 1. Here, we demonstrate that the known functional organization of the human immunodeficiency virus type 1 Rev trans activator is shared by the distantly related visna virus Rev protein. In particular, both Rev proteins contain an N-terminal domain marked by a highly basic core motif that determines RNA sequence specificity, as well as a second C-terminal domain containing an essential leucine-rich motif that functions as an activation domain. Chimeric proteins consisting of the binding domain of one Rev protein fused to the activation domain of the other were fully functional in the viral sequence context cognate for the binding domain. We also describe derivatives of visna virus Rev bearing a defective activation domain that displayed a trans-dominant negative phenotype in transfected cells. These visna virus Rev mutants may prove useful in the derivation of transgenic animals resistant to this agriculturally important retroviral pathogen.

Full text

PDF
3879

Images in this article

3878Image
on p.3878
3879Image
on p.3879
3880Image
on p.3880

Selected References

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

  1. Cullen B. R. Human immunodeficiency virus as a prototypic complex retrovirus. J Virol. 1991 Mar;65(3):1053–1056. doi: 10.1128/jvi.65.3.1053-1056.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Davis J. L., Clements J. E. Characterization of a cDNA clone encoding the visna virus transactivating protein. Proc Natl Acad Sci U S A. 1989 Jan;86(2):414–418. doi: 10.1073/pnas.86.2.414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Davis J. L., Molineaux S., Clements J. E. Visna virus exhibits a complex transcriptional pattern: one aspect of gene expression shared with the acquired immunodeficiency syndrome retrovirus. J Virol. 1987 May;61(5):1325–1331. doi: 10.1128/jvi.61.5.1325-1331.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fauci A. S. The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science. 1988 Feb 5;239(4840):617–622. doi: 10.1126/science.3277274. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Haase A. T. Pathogenesis of lentivirus infections. Nature. 1986 Jul 10;322(6075):130–136. doi: 10.1038/322130a0. [DOI] [PubMed] [Google Scholar]
  9. Hope T. J., McDonald D., Huang X. J., Low J., Parslow T. G. Mutational analysis of the human immunodeficiency virus type 1 Rev transactivator: essential residues near the amino terminus. J Virol. 1990 Nov;64(11):5360–5366. doi: 10.1128/jvi.64.11.5360-5366.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kim S. Y., Byrn R., Groopman J., Baltimore D. Temporal aspects of DNA and RNA synthesis during human immunodeficiency virus infection: evidence for differential gene expression. J Virol. 1989 Sep;63(9):3708–3713. doi: 10.1128/jvi.63.9.3708-3713.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lazinski D., Grzadzielska E., Das A. Sequence-specific recognition of RNA hairpins by bacteriophage antiterminators requires a conserved arginine-rich motif. Cell. 1989 Oct 6;59(1):207–218. doi: 10.1016/0092-8674(89)90882-9. [DOI] [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. Malim M. H., Cullen B. R. HIV-1 structural gene expression requires the binding of multiple Rev monomers to the viral RRE: implications for HIV-1 latency. Cell. 1991 Apr 19;65(2):241–248. doi: 10.1016/0092-8674(91)90158-u. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Mermer B., Felber B. K., Campbell M., Pavlakis G. N. Identification of trans-dominant HIV-1 rev protein mutants by direct transfer of bacterially produced proteins into human cells. Nucleic Acids Res. 1990 Apr 25;18(8):2037–2044. doi: 10.1093/nar/18.8.2037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Muesing M. A., Smith D. H., Cabradilla C. D., Benton C. V., Lasky L. A., Capon D. J. Nucleic acid structure and expression of the human AIDS/lymphadenopathy retrovirus. Nature. 1985 Feb 7;313(6002):450–458. doi: 10.1038/313450a0. [DOI] [PubMed] [Google Scholar]
  17. Mullis K. B., Faloona F. A. Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Methods Enzymol. 1987;155:335–350. doi: 10.1016/0076-6879(87)55023-6. [DOI] [PubMed] [Google Scholar]
  18. Olsen H. S., Cochrane A. W., Dillon P. J., Nalin C. M., Rosen C. A. Interaction of the human immunodeficiency virus type 1 Rev protein with a structured region in env mRNA is dependent on multimer formation mediated through a basic stretch of amino acids. Genes Dev. 1990 Aug;4(8):1357–1364. doi: 10.1101/gad.4.8.1357. [DOI] [PubMed] [Google Scholar]
  19. Ptashne M. How eukaryotic transcriptional activators work. Nature. 1988 Oct 20;335(6192):683–689. doi: 10.1038/335683a0. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Sonigo P., Alizon M., Staskus K., Klatzmann D., Cole S., Danos O., Retzel E., Tiollais P., Haase A., Wain-Hobson S. Nucleotide sequence of the visna lentivirus: relationship to the AIDS virus. Cell. 1985 Aug;42(1):369–382. doi: 10.1016/s0092-8674(85)80132-x. [DOI] [PubMed] [Google Scholar]
  22. Talbott R. L., Sparger E. E., Lovelace K. M., Fitch W. M., Pedersen N. C., Luciw P. A., Elder J. H. Nucleotide sequence and genomic organization of feline immunodeficiency virus. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5743–5747. doi: 10.1073/pnas.86.15.5743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tiley L. S., Brown P. H., Le S. Y., Maizel J. V., Clements J. E., Cullen B. R. Visna virus encodes a post-transcriptional regulator of viral structural gene expression. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7497–7501. doi: 10.1073/pnas.87.19.7497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Venkatesh L. K., Chinnadurai G. Mutants in a conserved region near the carboxy-terminus of HIV-1 Rev identify functionally important residues and exhibit a dominant negative phenotype. Virology. 1990 Sep;178(1):327–330. doi: 10.1016/0042-6822(90)90414-m. [DOI] [PubMed] [Google Scholar]
  25. Vigne R., Barban V., Quérat G., Mazarin V., Gourdou I., Sauze N. Transcription of visna virus during its lytic cycle: evidence for a sequential early and late gene expression. Virology. 1987 Nov;161(1):218–227. doi: 10.1016/0042-6822(87)90188-7. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES