| Upon infection of host cells by human immunodeficiency virus type 1 (HIV-1), the viral membrane fuses with the cell plasma membrane and the viral core is released into the cytoplasm, where uncoating of viral capsid (CA) core takes place. Numerous studies have shown that optimal core stability is a key determinant in the uncoating. However, the underlying factors and mechanisms governing uncoating are poorly understood. We have previously shown that HIV-1 integrase (IN) is involved in uncoating of the viral core and required for optimal core stability. In this study, we have demonstrated that IN interacts with in vitro assembled CA tubes and preferentially binds to CA hexamers. Our biochemical and biophysical analyses have further determined that the reaching dimer of IN is required for interacting with CA hexamer. Moreover, we show that both NTD and CTD of IN are involved in interacting with CA assemblies, while IN NTD contributes to the preferential recognition towards CA hexamers. This project provides useful information to understand crucial but yet poorly characterized processes during HIV-1 life cycle. By characterizing the IN-CA interaction, we may provide a mechanical basis for the requirement of IN during HIV-1 uncoating. The IN-CA interaction also indicates that IN may play a role during late stage of HIV-1 replication, as recent studies in the field suggested that IN may be involved in virion maturation. Finally, this finding highlights the potential for exploiting the CA and IN interaction as a new therapeutic target. |
