The human immunodeficiency virus (HIV) unspliced full length genomic RNA possesses features of an eukaryotic cellular mRNA as it is capped at its 5' end and polyadenylated at its 3' extremity. This genomic RNA is used both for the production of the viral structural and enzymatic proteins (Gag and Pol, respectively) and as genome for encapsidation in the newly formed viral particle. Although both of these processes are critical for viral replication, they should be controlled in a timely manner for a coherent progression into the viral cycle. Some of this regulation is exerted at the level of translational control and takes place on the viral 5' untranslated region and the beginning of the gag coding region. In this review, we have focused on the different initiation mechanisms (cap- and internal ribosome entry site (IRES)-dependent) that are used by the HIV-1 and HIV-2 genomic RNAs and the cellular and viral factors that can modulate their expression. Interestingly, although HIV-1 and HIV-2 share many similarities in the overall clinical syndrome they produce, in some aspects of their replication cycle, and in the structure of their respective genome, they exhibit some differences in the way that ribosomes are recruited on the gag mRNA to initiate translation and produce the viral proteins; this will be discussed in the light of the literature.
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