Human immunodeficiency virus type 1 reverse transcriptase

The Human Immunodeficiency Virus type 1 (HIV-1) is a retrovirus and a causative agent of the Acquired Immune Deficiency Syndrome (AIDS). Retroviruses are distinct from other viruses in their ability to encode an enzyme called reverse transcriptase (RT). The RT is the enzyme mainly involved in replication. It performs RNA- as well as DNA-dependent DNA synthesis in order to convert the single-stranded viral RNA genome into double-stranded DNA. The double-stranded DNA is stably integrated into the host cell genome and is used as a template for the production of a new viral generation. The HIV-1 RT is partially encoded by the POL open reading frame of the HIV-1 genome and consists of two subunits of 66 kDa (p66) and 51 kDa (p51). The p66 polypeptide encodes the reverse transcriptase and the RNase H domain. Half of the p66 molecules are further processed to generate the p51 protein with an identical N-terminus, but lacking the C-terminus which encodes the RNase H domain. In vivo both polypeptides are found in equimolar amounts thus forming a heterodimer. This dimerization is critical for the enzymatic activity. In this review we summarize (i) the replication cycle of HIV-1, (ii) the enzymatic properties of HIV-1 RT and (iii) the structure-function relationship of the HIV-1 RT in view of the known three dimensional structure.