HIV-1 REVERSE-TRANSCRIPTASE - AN OUT-OF-THE-ORDINARY ENZYME

Human immunodeficiency virus type 1 reverse transcriptase (HIV1 RT) is essential for virus replication. After cell infection, RT catalyses t he synthesis of the proviral genome, which is then integrated into the host cell genome. The present understanding of the origin of viral ge netic information variations following provirus synthesis is summarize d here. During reverse transcription, the structures of the primer-tem plate nucleic acid duplex (A, A-like and B forms), and the local helix bends, modulate RT DNA polymerizing activity by acting on kinetic par ameters of nucleotide incorporation and on enzyme processivity. Moreov er, the cellular microenvironment, such as dNTP pool imbalance, is inv olved in mutation fixation by directly influencing RT activity and vir al mutation rates. In addition to genome variations linked to RT activ ity, other parameters, like permanent viral replication and compartmen talization, contribute to HIV1 variability. The implications of these findings on therapy directed against HIV1 infection are discussed.