Integrated Simian Immunodeficiency Virus proviral DNA (SIV proviral DNA)

Integrated Simian Immunodeficiency Virus (SIV) proviral DNA is the double-stranded DNA intermediate of the SIV life cycle that is covalently integrated into the host cell genome by the viral integrase enzyme (PMID: 32997611). This integrated provirus serves as the template for viral transcription and constitutes the persistent viral reservoir that prevents a cure with standard antiretroviral therapy (ART), as it remains hidden from the immune system in a latent state (Nature Communications, 2020). In the context of therapeutic development, SIV proviral DNA is a primary target for gene-editing technologies like CRISPR/Cas9, which use guide RNAs to direct endonucleases to specific viral sequences such as the Long Terminal Repeats (LTRs) and the Gag gene (Excision BioTherapeutics, 2023). The goal of these interventions, exemplified by the investigational agent EBT-001, is to excise large segments of the proviral DNA to permanently inactivate the virus and potentially allow for ART-free remission (Gene Therapy, 2021). Monitoring the levels of integrated DNA in tissues like the lymph nodes and brain is a critical biomarker for assessing the efficacy of these curative strategies in non-human primate models (Journal of Virology, 2022).

Other names

SIV provirusIntegrated SIV DNASimian immunodeficiency virus reservoirSIV DNA

Targeted genomic excision and disruption of viral DNA sequences using site-specific endonucleases (e.g., CRISPR/Cas9) to eliminate the replication-competent viral reservoir.