Programmed —1 Ribosomal Frameshift in the Human Immunodeficiency Virus of Type 1
A programmed —1 ribosomal frameshift enables the human immunode-ficiency virus of type 1 (HIV-1) to produce its enzymes in a precise proportion relative to its structural proteins, which is necessary to control viral assembly and maturation. Here, we critically review models that account for this phenomenon, focusing on the most recent model, which postulates that the frameshift is triggered by an incomplete translocation and involves the slippage of three tRNAs. The effect of changes in the rate of translation initiation and elongation and the possible involvement of cellular factors in frameshifting are briefly examined. Finally, we highlight recent efforts intended to interfere with this type of frameshift as a strategy to develop novel anti-HIV drugs.
KeywordsSimian Immunodeficiency Virus Feline Immunodeficiency Virus Infectious Bronchitis Virus Stimulatory Signal Small Ribosomal Subunit
We thank Sergey Steinberg, Kevin Wilson and Steve Michnick for very stimulating discussions and for critical reading of this review. We are also grateful to Pascal Chartrand, Gerardo Ferbeyre, Nikolaus Heveker, Luis Rokeach and all the members of the Brakier-Gingras group for critical reading of this manuscript. Work from this laboratory that is cited herein was supported by the Canadian Institutes for Health Research.
- Baril M, Dulude D, Gendron K, Lemay G, Brakier-Gingras L (2003a) Efficiency of a programmed —1 ribosomal frameshift in the different subtypes of the human immunodeficiency virus type 1 group M. RNA 9:1246—1253Google Scholar
- Baril M, Dulude D, Steinberg SV, Brakier-Gingras L (2003b) The frameshift stimulatory signal of human immunodeficiency virus type 1 group O is a pseudoknot. J Mol Biol 331:571–583Google Scholar
- Gendron K, Charbonneau J, Dulude D, Heveker N, Ferbeyre G, Brakier-Gingras L (2008) The presence of the TAR RNA structure alters the programmed —1 ribosomal frameshift efficiency of the human immunodeficiency virus type 1 (HIV-1) by modifying the rate of translation initiation. Nucleic Acids Res 36:30–40PubMedCrossRefGoogle Scholar
- Gendron K, Dulude D, Lemay G, Ferbeyre G, Brakier-Gingras L (2005) The virion-associated Gag-Pol is decreased in chimeric Moloney murine leukemia viruses in which the readthrough region is replaced by the frameshift region of the human immunodeficiency virus type 1. Virology 334:342–352PubMedCrossRefGoogle Scholar
- Jacks T, Madhani HD, Masiarz FR, Varmus HE (1988a) Signals for ribosomal frameshifting in the Rous sarcoma virus gag-pol region. Cell 55:447–458Google Scholar
- Jacks T., Power MD, Masiarz FR, Luciw PA, Barr PJ, Varmus HE (1988b) Characterization of ribosomal frameshifting in HIV-1 gag-pol expression. Nature 331:280–283Google Scholar