The Human Immunodeficiency Virus type 1 (HIV-1) is a retrovirus responsible for the acquired immunodeficiency syndrome (AIDS). One of the critical enzymes in the HIV-1 lifecycle is the reverse transcriptase (RT), which is essential for converting the viral RNA genome into DNA, allowing it to integrate into the host cell’s genome. The HIV-1 reverse transcriptase is a heterodimer composed of two subunits: p66 and p51 .
The p66 subunit of HIV-1 reverse transcriptase is a 66 kDa protein encoded by the pol gene. It is glycosylated with N-linked sugars and produced using baculovirus vectors in insect cells . The p66 subunit possesses both RNA-dependent and DNA-dependent DNA polymerase activities, as well as RNase H activity, which are crucial for the reverse transcription process .
The p51 subunit, on the other hand, shares the same N-terminal sequence as p66 but lacks the C-terminal 140 amino acids. This structural difference makes p51 essential for providing structural and conformational stability to the RT enzyme .
HIV-1 reverse transcriptase can undergo post-translational modifications, which may play a significant role in regulating its activity. Major isoforms of the p66 and p51 subunits have been observed in virions and infected cells, suggesting that these modifications are important for the enzyme’s function inside the cell .
The recombinant HIV-1 p66 pol protein is widely used in research to study the mechanisms of reverse transcription and to develop antiretroviral drugs. Understanding the structure and function of this enzyme is crucial for designing inhibitors that can effectively target and block the reverse transcription process, thereby preventing the replication of the virus .