HIV-1 integrase enzyme (IN)

HIV-1 integrase is a 32 kDa viral enzyme essential for the HIV replication cycle, responsible for catalyzing the integration of the reverse-transcribed viral cDNA into the host cell genome[1][2][3][4][5][6]. It is encoded by the pol gene as part of a viral Gag-Pol polyprotein and is cleaved during virion maturation[5]. The integrase protein acts in a two-step process: 3'-processing (trimming viral DNA ends) and strand transfer (joining viral DNA to host DNA), both requiring divalent metal ions (Mg²⁺ or Mn²⁺) as cofactors[1][2][3][6]. Integrase is structurally composed of three domains: N-terminal (zinc-binding), catalytic core (contains the conserved DDE motif), and C-terminal (DNA-binding/stabilization)[1][2][3]. The enzyme functions as a multimer (tetramer) during integration and is the molecular target for the integrase strand transfer inhibitor (INSTI) class of antiretroviral drugs, which block the viral DNA integration step, halting viral replication and providing an effective therapeutic option for HIV-infected individuals[1][2][4][6]. Drug resistance mutations in the integrase gene are a significant concern for long-term therapy[4][6]. No human protein homolog exists, making integrase a highly selective antiviral target without direct host toxicity[1][4][6].

Other names

HIV-1 integraseHuman immunodeficiency virus type 1 integraseRetroviral integraseHIV-2 integrase

Inhibition of integrase strand transfer activity (prevents integration of HIV DNA into host genome) (Some investigational) Allosteric inhibition to block virion maturation