Retroviral reverse transcriptase: Structure, function and inhibition

Reverse transcriptase (RT) is a multifunctional enzyme that has RNA- and DNA-dependent DNA polymerase activity and ribonuclease H (RNase H) activity, and is responsible for the reverse transcription of retroviral single-stranded RNA into double-stranded DNA. The essential role that RT plays in the human immunodeficiency virus (HIV) life cycle is highlighted by the fact that multiple antiviral drugs-which can be classified into two distinct therapeutic classes-are routinely used to treat and/or prevent HIV infection. This book chapter provides detailed insights into the three-dimensional structure of HIV RT, the biochemical mechanisms of DNA polymerization and RNase H activity, and the mechanisms by which nucleoside/nucleotide and nonnucleoside RT inhibitors block reverse transcription.