HIV Integrase

Integrase (IN) is the HIV-1 enzyme, released from the Pol region of Gag-Pol, that inserts the reverse-transcribed viral DNA into host chromatin to establish infection. Acting as a multimer with cofactors LEDGF/p75 and viral DNA ends, it performs 3-prime processing of the viral DNA termini and then strand transfer into the host genome; cellular repair factors complete integration. Each catalytic domain carries a DDE motif coordinating divalent metal ions. Integrase strand-transfer inhibitors, including raltegravir, elvitegravir, dolutegravir and bictegravir, are first-line antiretrovirals, and allotropic inhibitors that block LEDGF binding are under investigation. Recombinant integrase enables strand-transfer assays, resistance studies and inhibitor discovery.