MicroRNAs and HIV-1 infection: antiviral activities and beyond

Cellular microRNAs (miRNAs) are an important class of small, non-coding RNAs that bind to host mRNAs based on sequence complementarity and regulate protein expression. They play important roles in controlling key cellular processes including cellular inception, differentiation and death. While several viruses have been shown to encode for viral miRNAs, controversy persists over the expression of a functional miRNA encoded in the human immunodeficiency virus type 1 (HIV-1) genome. However, it has been reported that HIV-1 infectivity is influenced by cellular miRNAs. Either through directly targeting the viral genome or by targeting host cellular proteins required for successful virus replication, multiple cellular miRNAs seem to modulate HIV-1 infection and replication. Perhaps as a survival strategy, HIV-1 may modulate proteins in the miRNA biogenesis pathway to subvert miRNA-induced antiviral effects. Global expression profiles of cellular miRNAs have also identified alterations of specific miRNAs post-HIV-1 infection both in vitro and in vivo (in various infected patient cohorts), suggesting potential roles for miRNAs in pathogenesis and disease progression. However, little attention has been devoted in understanding the roles played by these miRNAs at a cellular level. In this manuscript, we review past and current findings pertaining to the field of miRNA and HIV-1 interplay. In addition, we suggest strategies to exploit miRNAs therapeutically for curbing HIV-1 infectivity, replication and latency since they hold an untapped potential that deserves further investigation.