The HIV reverse transcriptase is known to have a notoriously high error rate. In fact, if your office photocopier was that sloppy, you’d probably end up doing your own version of the classic copier-smashing scene from the movie Office Space. But the shoddy workmanship of HIV’s genome-copying enzyme actually benefits the virus by allowing it to quickly evolve resistance to the immune system and drug therapies.
A team of researchers led by Michael McGrath at UCSF wondered if HIV’s genomic variability affected its miRNA sequences and, if so, how this might influence disease progression. So they analyzed 1293 sequences of a particular HIV miRNA derived from multiple tissues of seven HIV patients. The miRNA, called miR-H1, targets the transcript of the apoptosis antagonizing transcription factor (AATF). The researchers found that:
- Pre-miR-H1 sequences from different patients varied significantly
- Even within a single patient, pre-mIR-H1 sequences could vary considerably and even be deleted in some tissues
- Two patients with deleted or less stable miR-H1 had AIDS-related lymphoma, and a particular miR-H1 structure was observed in all patients with HIV-associated dementia
These results suggest that the miR-H1 gene is evolving rapidly, with the potential to either delete the miRNA or generate miRNA sequences with new cellular targets. Also, particular miR-H1 sequences might be linked with various AIDS-associated diseases. Go find a good copy of this paper for yourself at Biosystems, May, 2010.