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

HIV-1 integrase is a 32 kDa retroviral enzyme essential for the replication cycle of human immunodeficiency virus type 1 (HIV-1)[1][2][4][7]. It catalyzes the covalent insertion of viral DNA, synthesized by reverse transcriptase, into the host cell genome, a step crucial for stable infection and viral propagation[3][6]. The enzyme contains three domains: the N-terminal zinc-binding domain (facilitates tetramerization), a central catalytic core domain with a conserved DDE (Asp-Asp-Glu) motif responsible for catalysis, and a C-terminal SH3-like domain involved in nonspecific DNA binding[2][4][6]. Integration proceeds via a two-step reaction: 3′ processing, where integrase removes two nucleotides from each 3′ end of viral DNA, and strand transfer, in which the processed ends are joined to the host DNA[1][6]. Besides integration, integrase also binds to the viral RNA genome within virions, playing a crucial role in proper virion maturation and morphogenesis[3]. Targeting this enzyme has led to a class of antiretroviral drugs known as integrase strand transfer inhibitors (INSTIs), which are a mainstay in current HIV therapy regimens[2][7].

Other names

HIV-1 INretroviral integraseHIV integrase

Inhibition of integrase strand transfer activity (INSTI mechanism) Prevention of viral DNA integration into host chromosome Blocking proper maturation of virions by disrupting integrase–RNA interactions