Integrase
Integrase is a viral enzyme that inserts retroviral DNA into a host cell genome, creating a provirus.
What integrase is
Integrase is an enzyme produced by retroviruses that inserts viral DNA into the genome of an infected cell. In viruses such as HIV, integration is the step that turns a DNA copy of the viral RNA genome into a provirus. Once integrated, viral DNA can be copied with the host genome and transcribed by host machinery.
Where it fits in the life cycle
Integrase acts after reverse transcriptase has copied the viral RNA genome into double-stranded DNA. The viral DNA enters the nucleus as part of a preintegration complex. Integrase then processes the viral DNA ends and catalyzes their joining to host DNA. Host repair enzymes finish the junctions.
Two catalytic steps
Retroviral integration is usually described in two main catalytic steps. First, integrase performs 3-prime processing, trimming the viral DNA ends so they are ready for insertion. Second, it performs strand transfer, joining those processed viral DNA ends to phosphodiester bonds in host DNA.
Active site chemistry
Retroviral integrases share a catalytic core domain with conserved acidic residues often described as a DDE or D,D-35-E motif. These residues coordinate metal ions needed for DNA cutting and joining chemistry. Additional domains help bind viral DNA, multimerize, and interact with host or viral cofactors.
Integration site choice
Integration is not perfectly random. Different retroviruses show different preferences for genes, transcriptionally active chromatin, nucleosomes, or other genome features. Viral integrase proteins, host cofactors, chromatin structure, and nuclear entry pathways all help shape where proviruses land.
HIV integrase inhibitors
HIV treatment often includes drugs that block integrase strand transfer. These drugs prevent the stable insertion of viral DNA into host chromosomes, stopping a key step before productive proviral expression can occur. Resistance can arise through mutations, so integrase inhibitors are usually used in combination therapy.
Beyond HIV
Integrase-like systems appear in many mobile genetic elements. Retroviral integrases are related to transposases and other enzymes that move DNA segments. In biotechnology, integration is powerful because it can make inserted DNA stable, but uncontrolled integration can disrupt genes or regulatory regions.
Why it matters
Integrase matters because it is the molecular bridge between viral infection and permanent genetic insertion. It helps explain HIV latency, provirus formation, antiretroviral drug design, retroviral vector risks, and the evolutionary impact of viral DNA on host genomes.