Human Immunodeficiency Virus Type 1

HIV-1 the etiologic agent of AIDS does not encode any microRNAs, but HIV-1 mRNAs are predicted to contain targets for cellular microRNAs expressed in HIV-1 target cells, including T cells and macrophages. We are currently using molecular biology techniques to determine whether miRNA binding to the HIV-1 RNA genome actually occurs in infected human cells and to map these binding sites, if they exist. We will then use mutagenesis and other techniques to determine whether bound miRNAs help or hinder the HIV-1 life cycle. Data obtained so far suggest that HIV-1 has evolved to be largely resistant to inhibition by microRNAs, most likely by using RNA secondary structure to occlude microRNA binding sites. Of interest, we have recently demonstrated that HIV1 virions package low levels of microRNAs and that this process is selective, with some microRNAs being over- or underrepresented compared to the producer cell. This likely reflects microRNA binding to the viral genome, as inserted target sites for, for example, miR-155 result in a large increase in miR-155 virion incorporation. It remains unclear whether this serves any purpose, though inserted, accessible microRNA target sites do reduce virus infectivity, as does overexpression of the RISC component Ago2.