HIV genome is encoded by RNA, which is reverse-transcribed to DNA after entering a host cell. Then it is integrated into host's DNA, transcripted and translated to HIV proteins. HIV protease cleave them to produce mature infectious viruses, see Fig.1. The anti-HIV drugs have been developed to inhibit some enzymes essential for HIV replication, For example, HIV protease inhibitor are blocking the cleaving process so that it can only generate immature, non-infectious viral particles, see Fig.2. This leads to the successful development of HAART cocktail drug to combat HIV.
Fig.1 HIV infection process
Fig.2 How HIV inhibitor works
Xiaowei Zhuang's new research on HIV reverse transcriptase
The reverse transcriptase of human immunodeficiency virus (HIV) is never easy. it needs to discriminate a variety of nucleic-acid substrates such that active sites of the enzyme are correctly positioned to give the right DNA chain based on original RNA chain. How reverse transcriptase is doing not well-known. Zhuang Xiaowei's experiment shows how reverse transcriptase oriented itself with different nucleic-acid substrates. In article, it says "The enzyme adopted opposite binding orientations on duplexes containing DNA or RNA primers, directing its DNA synthesis or RNA hydrolysis activity, respectively. On duplexes containing the unique polypurine RNA primers for plus-strand DNA synthesis, the enzyme can rapidly switch between the two orientations. The switching kinetics were regulated by cognate nucleotides and non-nucleoside reverse transcriptase inhibitors, a major class of anti-HIV drugs. These results indicate that the activities of reverse transcriptase are determined by its binding orientation on substrates."[1]
Fig. 3 Zhuang's experiment set-up