HIV-1 integrase–viral DNA complex (HIV-1 IN–DNA complex)

The HIV-1 integrase–viral DNA complex, often called the intasome, is a protein–DNA assembly essential for viral replication. The complex consists of multiple copies of the viral integrase enzyme bound to the termini of double-stranded HIV DNA generated after reverse transcription. This intasome conducts two key reactions: 3'-end processing (removal of two nucleotides at each viral DNA terminus) and strand transfer (covalent insertion of the viral DNA into the host chromosome). Clinical drugs called integrase strand-transfer inhibitors (INSTIs) target this nucleoprotein complex to block viral integration and halt HIV replication. The DNA-bound form of integrase is the principal target for these drugs, which act by binding the active site and preventing strand transfer into host DNA. Resistance can occur through mutations in the integrase gene. Integration is a defining step in HIV pathogenesis, establishing lifelong infection unless therapeutically blocked.

Other names

HIV-1 intasomeHIV integrase-DNA complexHIV-1 pre-integration complex (PIC; though PIC may include additional cofactors)

Inhibition of strand transfer by binding to the integrase-DNA complex active site; most clinical inhibitors (INSTIs) block the insertion of viral DNA into host chromosomes. Many drugs act only on the DNA-bound form of integrase, not the free enzyme.