RNA Viruses: RNA Roles in Pathogenesis, Coreplication and Viral Load

Poltronieri, Palmiro; Sun, Binlian; Mallardo, Massimo

Recent reports studied several human miRNAs targeting HIV-1 sequences. Using target prediction software, five miRNA (miR-29a, miR-29b, miR-149, miR-324-5p, and miR-378) were found to target sequences, two of them located in the viral nef gene, of the HIV-1 genome [55] . miR-29a was shown to inhibit nef expression, and to repress HIV replication in Jurkat cells. Recently inhibition of HIV-1 infection by miR-29a and miR-29b was confirmed [56, 57] , however, HIV-1 is protected by a complex RNA secondary structure surrounding the target site. A different group of five miRNAs (miR-28, miR-125b, miR-150, miR-223, and miR-382) that target the 3'-UTR of the HIV genome was reported [58] . These "anti-HIV" miRNAs were shown to be enriched in resting CD4+ T cells and were hypothesized to be involved in proviral latency. In another study, four of these miRNAs were found responsible for differences between monocytes and macrophages in their permissivity to HIV infection [59] . Recently the action of miR-29, miR-133b, miR-138, miR-149 and miR-326, targeting HIV-1 sequences, was shown [60] . Therefore, in divergent cells and in varying contexts different miRNAs may selectively regulate HIV-1 infection through direct targeting viral sequences. Thus, a complex set of miRNA-mediated positive and negative regulatory events is influencing viral replication [51] . In monocytes, miR-1236 was shown to inhibit HIV-1 infection by repressing translation of cellular factor Vpr binding protein, VprBP/DCAF1 [61] . A significant number of host non-coding RNAs have been found in Hepatocellular carcinoma (HCC) caused by HCV infection, and are involved in pathogenesis of HCV and HCV-induced HCC [62] .