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. 1993 Dec;67(12):7317–7323. doi: 10.1128/jvi.67.12.7317-7323.1993

Identification of the activation domain of equine infectious anemia virus rev.

R A Fridell 1, K M Partin 1, S Carpenter 1, B R Cullen 1
PMCID: PMC238195  PMID: 8230455

Abstract

Several members of the lentivirus family of complex retroviruses have been shown to encode proteins that are functionally equivalent to the Rev posttranscriptional regulatory protein of human immunodeficiency virus type 1 (HIV-1). Furthermore, the domain organization of HIV-1 Rev, featuring a highly basic N-terminal RNA binding domain and a leucin-rich C-terminal effector domain, has also been shown to be highly conserved among Rev proteins derived from not only the primate but also the ovine and caprine lentiviruses. Although it has therefore appeared highly probable that the lentivirus equine infectious anemia virus (EIAV) also encodes a Rev, the predicted amino acid sequence of this putative EIAV regulatory protein does not display any evident homology to the basic and leucine-rich motifs characteristic of other known Rev proteins. By fusion of different segments of the proposed EIAV Rev protein to the well-defined RNA binding domain of either HIV-1 or visna virus Rev, we have identified a segment of this EIAV protein that can efficiently substitute in cis for the otherwise essential activation motif. Interestingly, the minimal EIAV Rev activation motif identified in this study comprises approximately 18 amino acids located toward the protein N terminus that lack any evident similarity to the leucine-rich activation domains found in these other lentivirus Rev proteins. It therefore appears that the Rev protein of EIAV, while analogous in function to Rev proteins defined in lentiviruses of primate, ovine, and caprine origin, is nevertheless distinguished by an entirely novel domain organization.

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Selected References

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  1. Böhnlein E., Berger J., Hauber J. Functional mapping of the human immunodeficiency virus type 1 Rev RNA binding domain: new insights into the domain structure of Rev and Rex. J Virol. 1991 Dec;65(12):7051–7055. doi: 10.1128/jvi.65.12.7051-7055.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Carpenter S., Alexandersen S., Long M. J., Perryman S., Chesebro B. Identification of a hypervariable region in the long terminal repeat of equine infectious anemia virus. J Virol. 1991 Mar;65(3):1605–1610. doi: 10.1128/jvi.65.3.1605-1610.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carroll R., Derse D. Translation of equine infectious anemia virus bicistronic tat-rev mRNA requires leaky ribosome scanning of the tat CTG initiation codon. J Virol. 1993 Mar;67(3):1433–1440. doi: 10.1128/jvi.67.3.1433-1440.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carroll R., Martarano L., Derse D. Identification of lentivirus tat functional domains through generation of equine infectious anemia virus/human immunodeficiency virus type 1 tat gene chimeras. J Virol. 1991 Jul;65(7):3460–3467. doi: 10.1128/jvi.65.7.3460-3467.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chang D. D., Sharp P. A. Regulation by HIV Rev depends upon recognition of splice sites. Cell. 1989 Dec 1;59(5):789–795. doi: 10.1016/0092-8674(89)90602-8. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Dillon P. J., Nelbock P., Perkins A., Rosen C. A. Function of the human immunodeficiency virus types 1 and 2 Rev proteins is dependent on their ability to interact with a structured region present in env gene mRNA. J Virol. 1990 Sep;64(9):4428–4437. doi: 10.1128/jvi.64.9.4428-4437.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dillon P. J., Nelbock P., Perkins A., Rosen C. A. Structural and functional analysis of the human immunodeficiency virus type 2 Rev protein. J Virol. 1991 Jan;65(1):445–449. doi: 10.1128/jvi.65.1.445-449.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dorn P., DaSilva L., Martarano L., Derse D. Equine infectious anemia virus tat: insights into the structure, function, and evolution of lentivirus trans-activator proteins. J Virol. 1990 Apr;64(4):1616–1624. doi: 10.1128/jvi.64.4.1616-1624.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Eustice D. C., Feldman P. A., Colberg-Poley A. M., Buckery R. M., Neubauer R. H. A sensitive method for the detection of beta-galactosidase in transfected mammalian cells. Biotechniques. 1991 Dec;11(6):739-40, 742-3. [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. Garrett E. D., Cullen B. R. Comparative analysis of Rev function in human immunodeficiency virus types 1 and 2. J Virol. 1992 Jul;66(7):4288–4294. doi: 10.1128/jvi.66.7.4288-4294.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hope T. J., Bond B. L., McDonald D., Klein N. P., Parslow T. G. Effector domains of human immunodeficiency virus type 1 Rev and human T-cell leukemia virus type I Rex are functionally interchangeable and share an essential peptide motif. J Virol. 1991 Nov;65(11):6001–6007. doi: 10.1128/jvi.65.11.6001-6007.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hope T. J., Huang X. J., McDonald D., Parslow T. G. Steroid-receptor fusion of the human immunodeficiency virus type 1 Rev transactivator: mapping cryptic functions of the arginine-rich motif. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7787–7791. doi: 10.1073/pnas.87.19.7787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kalinski H., Yaniv A., Mashiah P., Miki T., Tronick S. R., Gazit A. rev-like transcripts of caprine arthritis encephalitis virus. Virology. 1991 Aug;183(2):786–792. doi: 10.1016/0042-6822(91)91012-6. [DOI] [PubMed] [Google Scholar]
  18. Kawakami T., Sherman L., Dahlberg J., Gazit A., Yaniv A., Tronick S. R., Aaronson S. A. Nucleotide sequence analysis of equine infectious anemia virus proviral DNA. Virology. 1987 Jun;158(2):300–312. doi: 10.1016/0042-6822(87)90202-9. [DOI] [PubMed] [Google Scholar]
  19. Kiyomasu T., Miyazawa T., Furuya T., Shibata R., Sakai H., Sakuragi J., Fukasawa M., Maki N., Hasegawa A., Mikami T. Identification of feline immunodeficiency virus rev gene activity. J Virol. 1991 Aug;65(8):4539–4542. doi: 10.1128/jvi.65.8.4539-4542.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kjems J., Frankel A. D., Sharp P. A. Specific regulation of mRNA splicing in vitro by a peptide from HIV-1 Rev. Cell. 1991 Oct 4;67(1):169–178. doi: 10.1016/0092-8674(91)90580-r. [DOI] [PubMed] [Google Scholar]
  21. Kubota S., Siomi H., Satoh T., Endo S., Maki M., Hatanaka M. Functional similarity of HIV-I rev and HTLV-I rex proteins: identification of a new nucleolar-targeting signal in rev protein. Biochem Biophys Res Commun. 1989 Aug 15;162(3):963–970. doi: 10.1016/0006-291x(89)90767-5. [DOI] [PubMed] [Google Scholar]
  22. Lu X. B., Heimer J., Rekosh D., Hammarskjöld M. L. U1 small nuclear RNA plays a direct role in the formation of a rev-regulated human immunodeficiency virus env mRNA that remains unspliced. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7598–7602. doi: 10.1073/pnas.87.19.7598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. 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]
  26. 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]
  27. Malim M. H., McCarn D. F., Tiley L. S., Cullen B. R. Mutational definition of the human immunodeficiency virus type 1 Rev activation domain. J Virol. 1991 Aug;65(8):4248–4254. doi: 10.1128/jvi.65.8.4248-4254.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Malim M. H., Tiley L. S., McCarn D. F., Rusche J. R., Hauber J., Cullen B. R. HIV-1 structural gene expression requires binding of the Rev trans-activator to its RNA target sequence. Cell. 1990 Feb 23;60(4):675–683. doi: 10.1016/0092-8674(90)90670-a. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Phillips T. R., Lamont C., Konings D. A., Shacklett B. L., Hamson C. A., Luciw P. A., Elder J. H. Identification of the Rev transactivation and Rev-responsive elements of feline immunodeficiency virus. J Virol. 1992 Sep;66(9):5464–5471. doi: 10.1128/jvi.66.9.5464-5471.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rasty S., Dhruva B. R., Schiltz R. L., Shih D. S., Issel C. J., Montelaro R. C. Proviral DNA integration and transcriptional patterns of equine infectious anemia virus during persistent and cytopathic infections. J Virol. 1990 Jan;64(1):86–95. doi: 10.1128/jvi.64.1.86-95.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Rushlow K., Olsen K., Stiegler G., Payne S. L., Montelaro R. C., Issel C. J. Lentivirus genomic organization: the complete nucleotide sequence of the env gene region of equine infectious anemia virus. Virology. 1986 Dec;155(2):309–321. doi: 10.1016/0042-6822(86)90195-9. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Stephens R. M., Derse D., Rice N. R. Cloning and characterization of cDNAs encoding equine infectious anemia virus tat and putative Rev proteins. J Virol. 1990 Aug;64(8):3716–3725. doi: 10.1128/jvi.64.8.3716-3725.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. 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]
  36. Tiley L. S., Cullen B. R. Structural and functional analysis of the visna virus Rev-response element. J Virol. 1992 Jun;66(6):3609–3615. doi: 10.1128/jvi.66.6.3609-3615.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Tiley L. S., Malim M. H., Cullen B. R. Conserved functional organization of the human immunodeficiency virus type 1 and visna virus Rev proteins. J Virol. 1991 Jul;65(7):3877–3881. doi: 10.1128/jvi.65.7.3877-3881.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. 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]
  39. Weichselbraun I., Farrington G. K., Rusche J. R., Böhnlein E., Hauber J. Definition of the human immunodeficiency virus type 1 Rev and human T-cell leukemia virus type I Rex protein activation domain by functional exchange. J Virol. 1992 Apr;66(4):2583–2587. doi: 10.1128/jvi.66.4.2583-2587.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Zapp M. L., Hope T. J., Parslow T. G., Green M. R. Oligomerization and RNA binding domains of the type 1 human immunodeficiency virus Rev protein: a dual function for an arginine-rich binding motif. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7734–7738. doi: 10.1073/pnas.88.17.7734. [DOI] [PMC free article] [PubMed] [Google Scholar]

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