Insights into the functions of a molecular Swiss army knife: the intasome structure reveals inhibitor action

Abstract

Evaluation of: Hare S, Gupta SS, Valkov E, Engelman A, Cherepanov P: Retroviral intasome assembly and inhibition of DNA strand transfer. Nature 464(7286), 232–236 (2010). During HIV replication, integrase is responsible for the integration of the cDNA copy of the viral RNA genome into the host chromatin. In the recent history of anti-HIV therapy integrase has become an established drug target for HAART, but development of second-generation integrase inhibitors has been hampered by the lack of structural information. Hare et al. have now described the full-length integrase structure of a distant cousin of HIV-1, the prototype foamy virus. This insight into the mechanism of catalysis will boost the rational design of second-generation strand-transfer inhibitors.