HIV pol Expression via a Ribosomal Frameshift

  • Alan J. Kingsman
  • Wilma Wilson
  • Susan M. Kingsman
Conference paper
Part of the NATO ASI Series book series (volume 49)


The genetic relationships of the gag and pol genes of all retroviruses are approximately the same and the strategy for expression of the protein products of these genes is also strongly conserved (Weiss et al., 1982) (e.g. Figure 1). The gag and pol genes are adjacent and in many cases the 3′ end of gag and the 5′ end of pol overlap by up to a few hundred nucleotides. Where there is an overlap pol is generally in the -1 translational phase with respect to gag. Both genes are expressed from the full length genomic RNA to produce two primary translation products, a GAG precursor protein and a GAG:POL fusion precursor protein. The production of the fusion protein is achieved by the gag and pol reading frames being brought into translational phase. For several years it was assumed that this translational shift was mediated by a splice and the absence of any evidence for this was explained by proposing that the splice was small and therefore hard to detect (Weiss et al., 1 982). However, in 1985 two pieces of data suggested that the splicing hypothesis was wrong. First, in the retrovirus-like yeast transposon Ty it was shown that frameshifting between the TYA gene, a gag analogue, and the TYB gene, a pol analogue, was not due to splicing (Mellor et al., 1985; Clare and Farabaugh, 1985).


Bovine Leukemia Virus Mouse Mammary Tumor Virus Equine Infectious Anemia Virus Rous Sarcoma Virus Ribosomal Frameshifting 
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  1. Brierley, I., Digard, P. and Inglis, S. C. (1989). Characterization of an efficient coronavirus ribosomal frameshifting signal: requirement for an RNA pseudoknot. Cell 52, 537–547.CrossRefGoogle Scholar
  2. Chakrabarti, L., Guyader, M., Alizon, M., Daniel, M. D., Desrosiers, R. C., Tiollais, P. and Sonigo, P. (1987). Sequence of simian immunodeficiency virus from macaque and its relationship to other human and simian retroviruses. Nature 328, 543–547.PubMedCrossRefGoogle Scholar
  3. Clare, J. and Farabaugh, P. (1985) Nucleotide sequence of a yeast Ty element: evidence for an unusual mechanism of gene expression. Proc. Natl. Acad. Sci. USA 82, 2829–2833.PubMedCrossRefGoogle Scholar
  4. Clare, J. J., Belcourt, M. and Farabaugh, P. J. (1988). Efficient translational frameshifting occurs within a conserved sequence of the overlap between the two genes of a yeast Ty1 transposon. Proc. Natl. Acad. Sci. USA 85, 681 6–6820.Google Scholar
  5. Craigen, W. J. and Caskey, C. T. (1986). Expression of peptide chain release factor 2 requires high-efficiency frameshift. Nature 332, 273–275.CrossRefGoogle Scholar
  6. Curran, J. F. and Yarus, M. (1988). Use of tRNA suppressors to probe regulation of Escherichia QQ.11 release factor 2. J. Mol. Biol. 203, 75–83.PubMedCrossRefGoogle Scholar
  7. Guyader, M., Emerman, M., Sonigo, P., Claver, F., Montagnier, L. and Alizon, M. (1987). Genome organization and transcription of the human immunodeficiency virus type 2. Nature 326, 662–669.PubMedCrossRefGoogle Scholar
  8. Hiramatsu, K, Nishida, J., Naito, A. and Koshikura, H. (1987). Molecular cloning of the closed circular provirus of human T cell leukemia virus type 1: a new open reading frame in the gag-pol region. J.Gen. Virol. 68, 213–218.PubMedCrossRefGoogle Scholar
  9. Jacks, T. and Varmus, H. E. (1985). Expression of the Rous sarcoma virus pjal gene by ribosomal frameshif ting. Science 230, 1237–1242.PubMedCrossRefGoogle Scholar
  10. Jacks, T., Townsley, K., Varmus, H. E. and Majors, J. (1987). Two efficient ribosomal frameshifting events are required for synthesis of mouse mammary tumor virus sag-related polyproteins. Proc. Natl. Acad. Sci. USA 84, 4398–4302.CrossRefGoogle Scholar
  11. Jacks, T., Power, M. D., Masiarz, F. R., Luciw, P. A., Barr, P. J. and Varmus, H. E. (1988a). Characterization of ribosomal frameshifting in HIV-1 gag-pol expression. Nature 331, 280–283.PubMedCrossRefGoogle Scholar
  12. Jacks, T., Madhani, H. D., Masiarz, F. R. and Varmus, H. E. (1988b). Signals for ribosomal frameshifting in the Rous sarcoma virus gag-pol region. Cell 55, 447–458.PubMedCrossRefGoogle Scholar
  13. Madhani, H. D., Jacks, T. and Varmus, H. E. (1988). Signals for the expression of the HIV pal gene by ribosomal frameshifting. In The Control of HIV pol Gene Expression, R.Franza, B.Cullen and F.Wong-Staal,eds. (Cold Spring Harbor, New York: Cold Spring Harbor Laboratory ), pp. 119–125.Google Scholar
  14. Mador, N., Panet, A and Honigman, A. (1989). Translation of gag, prof and pol gene products of human T-cell leukemia virus type 2. J.Virol. 63, 2400–2404.PubMedGoogle Scholar
  15. Marlor, R. L. Parkhurst, S. M. and Corces, V. G. (1986). The Drosophila melanogaster gypsy transposable element encodes putative gene products homologous to retroviral proteins. Mol. Cell. Biol. 6, 1129–1134.Google Scholar
  16. Meitz, J. A., Grossman, Z., Leuders, K. K. and Kuff, E. L. (1987). Nucleotide sequence of a complete mouse intracisternal A-particle genome: no relationship to known aspects of particle assembly and function. J. Virol. 61, 3020–3029.Google Scholar
  17. Mellor, J., Fulton, A. M., Dobson, M. J., Wilson, W., Kingsman, S. M. and Kingsman, A. J. (1985). A retrovirus-like strategy for expression of a fusion protein encoded by the yeast transposon, Ty1. Nature 313, 243–246.PubMedCrossRefGoogle Scholar
  18. Moore, R., Dixon, M. Smith, R., Peters, G. and Dickson, C. (1987). Complete nucleotide sequence of a milk-transmitted mouse mammary tumor virus; two frameshift suppression events are required for translation of gag and pol. J. Virol. 61, 480–490.Google Scholar
  19. Power, M. D. Marx, P. A. Bryant, M. L., Gardner, M. D., Barr, P. J. and Luciw, P. A. (1986). Nucleotide sequence of SRV-1, a type D simian acquired immune deficiency syndrome retrovirus. Science 231, 1567–1572.PubMedCrossRefGoogle Scholar
  20. 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., Ivanoff, L., Petteway, Jr., S. R. Pearson, M. L., Lautenberger, J. A., Papas, T. S., Ghrayeb, J., Chang, N. T., Gallo, R. C. and Wong-Staal, F. (1985). Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature 211, 277–284.Google Scholar
  21. Rice, C. M. and Strauss, J. H. (1981). Nucleotide sequence of the 26S mRNA of sindbis virus and deduced sequence of the encoded virus structural proteins Proc. Natl. Acad. Sci. USA 78, 1062–1066.CrossRefGoogle Scholar
  22. Sagata, N., Yasunaga, T., Tsuzuku-Kawamura, J., Ohishi, K., Ogawa, Y. and Ikawa, Y. (1985). Complete nucleotide sequence of the genome of bovine leukemia virus: its evolutionary relationship to other retroviruses. Proc. Natl. Acad. Sci. USA 82, 677–681.PubMedCrossRefGoogle Scholar
  23. Saigo, K., Kugimiya, W., Matsuo, Y., Inouye, S., Koshioka, K. and Yuki, S. (1984). Identification of the coding sequence for a reverse transcriptase-like enzyme in a transposable genetic element in Drosophila melanogaster. Nature 312, 659–661.PubMedCrossRefGoogle Scholar
  24. Sanchez-Pescador, R., Power, M. D., Barr, P. J., Steimer, K. S., Stempien, M. M., Brown-Shimmer, S. L., Gee, W. W., Renard, A., Randolph, A., Levy, J. A., Dina, D. and Luciw, P. A. (1985). Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-2). Science 221, 484–492.CrossRefGoogle Scholar
  25. Schwartz, D. E., Tizard, R. and Gilbert, W. (1983). Nucleotide sequence sequence of Rous sarcoma virus. Cell 22, 853–869.CrossRefGoogle Scholar
  26. Shimotohno, K., Takahashi, Y., Shimizu, N., Gojobori, T., Golde, D. W., Chen, I. S. Y., Miwa, M. and Sugimura, T. (1985). Complete nucleotide sequence of an infectious clone of human T-cell leukemia virus type II: an open reading frame for the protease gene. Proc. Natl. Acad. Sci. USA 82, 3101–3105.PubMedCrossRefGoogle Scholar
  27. Sonigo, P., Alizon, M., Staskus, K., Klatzmann, D., Cole, S., Danos, O., Retzel, E., Tiollais, P., Haase, A. and Wain-Hobson, S. (1985). Nucleotide sequence of the visna lentivirus: relationship to the AIDS virus. Cell 42, 369–382.PubMedCrossRefGoogle Scholar
  28. Sonigo, P., Barker, C., Hunter, E. and Wain-Hobson, S. (1986). Nucleotide sequence of Mason Pfizer monkey virus: an immunosuppressive D-type retrovirus. Cell, 45, 375–385.PubMedCrossRefGoogle Scholar
  29. Stephens, R. M., Casey, J. W. and Rice, N. R. (1986). Equine infectious anemia virus gag and pol genes: relatedness to visna and AIDS virus. Science 231, 589–594.PubMedCrossRefGoogle Scholar
  30. Wain-Hobson, S., Sonigo, P., Danos, O., Cole, S. and Alizon, M. (1985). Nucleotide sequence of the AIDS virus, LAV. Cell 40, 9–17.CrossRefGoogle Scholar
  31. Weiss, R., Teich, N., Varmus, H. and Coffin, J. (1 982). Molecular Biology of Tumor Viruses. (Cold Spring Harbor, New York: Cold Spring Harbor Laboratory).Google Scholar
  32. Wilson, W., Malim, M. H., Mellor, J., Kingsman, A. J. and Kingsman, S. M. (1986) Expression strategies of the yeast transposon Ty: a short sequence directs ribosomal frameshifting. Nucl. Acids Res. 14, 7001–7015.PubMedCrossRefGoogle Scholar
  33. Wilson, W., Braddock, M., Adams, S. E., Rathjen, P. D., Kingsman, S. M. and Kingsman, A. J. (1988). HIV expression strategies: ribosomal frameshifting is directed by a short sequence in both mammalian and yeast systems. Cell 55., 1159–1169.PubMedCrossRefGoogle Scholar
  34. Yoshinaka, Y., Katoh, I., Copeland, T.D. and Oroszlan, S. (1985) Murine leukaemia virus protease is encoded by the gag-pol gene and is synthesised through suppression of an amber termination codon. Proc. Natl. Acad. Sci. USA 82, 1618–1622.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • Alan J. Kingsman
    • 1
  • Wilma Wilson
    • 1
  • Susan M. Kingsman
    • 1
  1. 1.Department of BiochemistryOxfordUK

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