Effect of the RNAi pathway on HIV-1 infection and replication

microRNA (miRNA) are 18-25 nucleotides small RNAs that regulate gene expression at the posttranscriptional level. They are expressed in many plants and animal species including humans. miRNAs are involved in the regulation of developmental timing, proliferation, apoptosis, signal transduction and differentiation. miRNAs and the small interfering RNA (siRNA) mediate RNA interference (RNAi) in cells although their biogenesis are different. Some viruses also encode their own miRNAs but the targets of many of the viral-encoded miRNAs are still largely unknown. miRNAs have recently been shown to regulate viral infections. The research described in this thesis aims at deciphering the influence of RNAi on HIV-1 infection and pathogenesis. In addition, we also examined how HIV infection may affect miRNA expression profiles in target cells. HIV-1 infection led to a differential miRNA expression profile compared to that of uninfected cells. A VPR mutant of HIV-1 also gave a different miRNA expression profile compared to the uninfected cells. This suggested that HIV-1 infection affects the cellular miRNA mechanism and that HIV-1 genes may exert different effects on RNAi. The impact of abrogating RNAi on HIV-1 infection was determined by downregulating Dicer, a critical component of the RNAi pathway. Transient Dicer knockdown did not have any noticeable effect on HIV-1.