Étude des mécanismes non-conventionnels de traduction chez le virus de l'immunodéficience humaine de type 1 et le virus de l'hépatite C

Content Provider	Semantic Scholar
Author	Baril, Martin
Copyright Year	2005
Abstract	Human immunodeficiency virus type 1 (HIV-1) and Hepatitis C virus (HCV) are responsible for two major viral pandernics and around 40 and 200 million people, respectively, are infected with these viruses worldwide. During the course of my Ph.D. studies, I investigated unconventional translation mechanisms used by these two viruses. One of these unconventional translation mechanisrns is a programmed —1 ribosornal frameshift that is used by HIV1. In HIV1, Gag, the precursor of the viral structural proteins, and Pol, the precursor of the viral enzymes, are synthesized from the saine RNA, i.e. the full-length viral RNA, but the coding sequence of Pol is in a —1 reading frame relative to the coding sequence of Gag. The majority of ribosornes translate the viral RNA according to conventional rules and synthesize Gag, but a minority of ribosomes that initiated translation at the initiation codon of Gag shifi the reading frame at a specific sequence before they encounter the stop codon of Gag and extend the translation to the pot gene, synthesizing Gag-Pol. The expression of Pol is thus regulated by a —1 frameshifi and the efficiency of this —l frameshifi event controls the Gag-Pol to Gag ratio, which is critical for particle assembly, replication and viral infectivity. This —Ï frameshifi requires two cis acting elements in the viral mRNA: a slippery sequence, where ribosomes slip by one nucleotide in the 5’ direction, and a downstrearn stimulatory signal, which is a specific structure that controls the —1 frarneshifi efficiency. Our group had previously dernonstrated that the —l frameshifi stirnulatory signal ofthe subtype B of group M ofHIV-1 (the group M is predorninant worldwide and the subtype B is the rnost widespread in America and Europe) is a two-stem helix, in which a three-purine bulge interrupts the two stems. Our studies showed that the —1 frameshifi stimulatory signal of all the other subtypes of group M can be folded into the same structure as in subtype B, despite sequence variations. Wc also showed that the efficiency of the —1 frameshifi of every subtype of group M falis within a nanow window, the maximal deviation from the mean value of the efficiency of these subtypes being 35%. Our results confirmed the importance of the Gag-Pol to Gag
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