Integrated Human Immunodeficiency Virus proviral DNA (HIV proviral DNA) (HIV proviral DNA)

Integrated Human Immunodeficiency Virus (HIV) proviral DNA is the double-stranded DNA sequence synthesized from the viral RNA genome and subsequently inserted into the host cell's nuclear DNA (PMID: 30696983). This integration is a defining step in the HIV life cycle, mediated by the viral enzyme integrase, and establishes a permanent infection within the host (PMID: 22835941). The provirus serves as the template for all subsequent viral transcription and replication; however, in a subset of cells, it enters a latent state where it remains transcriptionally silent and invisible to the immune system (PMID: 25241201). This latent reservoir is the primary barrier to a definitive cure, as it persists despite suppressive antiretroviral therapy (ART) and can spontaneously reactivate (PMID: 26351141). Therapeutic interventions targeting the provirus include latency-reversing agents (LRAs) to induce viral expression for immune-mediated clearance, transcriptional inhibitors to enforce permanent silencing, and gene-editing tools like CRISPR/Cas9 to physically excise the viral sequence (NCT05144386). Monitoring the proviral reservoir is typically achieved through specialized assays like the Intact Proviral DNA Assay (IPDA), which distinguishes between defective and replication-competent proviruses (PMID: 30696983). Successfully targeting and eliminating or permanently silencing integrated proviral DNA is considered the primary goal for achieving a functional or sterilizing cure for HIV/AIDS.

Other names

HIV provirusIntegrated HIV-1 DNALatent HIV reservoirHIV-1 proviral DNA

Therapeutic strategies include latency reversal (shock and kill) using HDAC inhibitors to induce viral expression, transcriptional silencing (block and lock) to permanently suppress the provirus, and direct excision using gene-editing technologies like CRISPR/Cas9 (PMID: 22835941, PMID: 30696983, NCT05144386).