Two personalities of HIV-1 integrase

HIV-1 integrase is responsible for the irreversible insertion of the reverse-transcribed viral genome into a host cell chromosome. To fulfill this function, integrase binds both ends of the viral DNA molecule, forming the intasome, a highly stable nucleoprotein complex. The HIV-1 intasome is the target of clinically approved integrase strand transfer inhibitors, such as dolutegravir and bictegravir.

In addition to its well-characterized enzymatic function, HIV-1 integrase plays an essential role in packaging viral genomic RNA within compact, conical cores during viral maturation. Recently, we determined high-resolution structures of a primate lentiviral integrase in complex with RNA and visualized the corresponding assemblies within native mature HIV-1 cores. The structures revealed that integrase forms an ordered linear filament composed of repeating octameric units stabilized by interactions with RNA. Within native cores, the ribonucleoprotein filament extends along the inner surface of the capsid lattice, with each integrase octamer spanning a pair of capsid hexamers and interacting with their major homology regions.