HIV-miR-H1 evolvability during HIV pathogenesis.

The discovery of microRNAs (miRNAs) in viruses has generated considerable attention into their functional relevance in processes such as cell death, viral proliferation, and oncogenesis. Two early studies found no detectable miRNAs expressed within HIV; however, several studies have verified the existence and function of three HIV miRNAs, most notably HIV-miR-TAR, thus making the earlier results controversial. Although miRNAs are highly conserved within most species, HIV is known to have a high mutation rate, which could contribute to the opposing experimental findings and raises questions about whether all HIV miRNAs are robust enough to maintain their integrity, especially in viral regions prone to insertions and deletions. In addition, could the evolvability of HIV miRNAs contribute to the diversity in HIV disease pathogenesis? To address this question, we examined mutations in 1293 sequences in a suspect HIV miRNA, called miR-H1, derived from a large variety of tissues from seven patients. We found considerable diversity within the structures, including a patient-specific deletion and the potential for the development of new miRNAs as a result of deletions. We also note a potential disease association between a less stable miR-H1 and the development of AIDS-related lymphoma (ARL).