Human immunodeficiency virus reverse transcriptase

Abstract

Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is an essential enzyme for HIV replication which converts the single-stranded viral RNA into a double-stranded DNA, suitable for integration into the host cell genome (Telesnitsky and Goff 1997). Heterodimeric p66/p51 HIV-1 RT (Fig. 19.1) has both synthetic (DNA polymerase) and degradative activities (ribonuclease H or RNase H), located at the N- and C-terminus of its p66 subunit, respectively. During HIV-1 replication, a complicated series of protein-protein and protein-nucleic acid interactions occur, each with the potential to be targeted by a small-molecule antagonist which might be developed into a potent therapeutic agent. Given the problem of increasing resistance against anti-HIV drugs currently in clinical use and the continued need to identify new drug targets, enzymatic activities and interactions, protein folding, and disruption of nucleic-acid structure are areas where detailed studies promise to unveil novel approaches with the potential for therapeutic intervention.