miR-122 promotion of the hepatitis C virus life cycle: sound in the silence.

The unusual role for miR-122 in promoting the hepatitis C virus (HCV) life cycle was first identified in 2005, but its mechanism of action remains uncharacterized. The virus appears to use the microRNA (miRNA) in a way that is opposed to that of normal miRNAs. Instead of interacting with sequences in the 3'-untranslated region (UTR), miR-122 binds to two sites in the 5'-UTR, and instead of silencing gene expression or promoting the degradation of the viral RNA, it stabilizes the genome and potently augments the efficiency by which HCV RNA accumulates in infected cells. This review discusses the current knowledge and models for the mechanism by which miR-122 promotes the HCV life cycle. Annealing of miR-122 to the HCV genome requires particular base pairing, stimulates translation, and stabilizes the viral genome by blocking degradation by host exonucleases, but these functions are unlikely to be the whole story. We will discuss other possible functions for miR-122, the stages of the HCV life cycle at which miR-122 may influence HCV, and other related viruses that may be similarly regulated by miR-122. Despite our lack of detailed mechanistic information, antagonism of miR-122 is emerging as a powerful method to inhibit HCV infections, and unique to other HCV treatment strategies does not, thus far, appear to induce emergence of escape mutants. Used alone or in combination with other antiviral drugs, miR-122 antagonists could be useful to both inhibit the virus and provide selective pressure to inhibit the development of resistance.