Human immunodeficiency virus type 1 integrase (HIV-1 IN) (HIV-1 IN)

Human immunodeficiency virus type 1 (HIV-1) integrase is a 32 kDa protein encoded by the viral pol gene, essential for the permanent integration of viral DNA into the host cell genome (UniProt P03366). The enzyme functions as part of a higher-order nucleoprotein complex known as the intasome, which stabilizes the viral DNA ends during the integration process (PubMed: 28234330). Integration occurs via two primary catalytic steps: 3'-processing, where two nucleotides are removed from the viral DNA ends, and strand transfer, where the processed ends are covalently joined to the host DNA. The strand transfer step is the primary target of Integrase Strand Transfer Inhibitors (INSTIs), which are a cornerstone of modern antiretroviral therapy (NIH: HIVinfo). These drugs, including dolutegravir and bictegravir, bind specifically to the integrase-viral DNA complex, blocking the catalytic site and preventing the establishment of the provirus. Resistance to these drugs typically arises through specific mutations within the integrase gene that alter the binding pocket while maintaining catalytic function (PubMed: 30103470).

Other names

HIV-1 integraseIntegrasePol integrasep31HIV-1 IN strand transfer complex

Integrase strand transfer inhibitors (INSTIs) bind to the active site of the integrase enzyme when it is complexed with viral DNA (the intasome), chelating the essential Mg2+ ions and preventing the covalent insertion of viral DNA into the host genome.