Human immunodeficiency virus type 1 provirus (HIV-1 provirus)

The Human immunodeficiency virus type 1 (HIV-1) provirus is the double-stranded DNA form of the viral genome that has been integrated into the host cell's chromosomal DNA by the viral enzyme integrase (Nature Reviews Microbiology, 2015, doi:10.1038/nrmicro3444). It serves as the definitive template for the production of new viral particles, hijacking the host's transcriptional machinery to express viral proteins (NIH NIAID, 2023). While antiretroviral therapy (ART) can suppress active replication, it cannot eliminate the provirus, which can persist in a transcriptionally silent or latent state within long-lived resting CD4+ T cells (Journal of Virology, 2019, doi:10.1128/JVI.01345-18). This latent reservoir is the primary barrier to a sterile cure for HIV, as the virus can rebound if ART is discontinued. Therapeutic strategies targeting the provirus include 'shock and kill' approaches using latency-reversing agents like Vorinostat to induce viral expression, 'block and lock' methods to permanently silence the promoter, and gene-editing tools like CRISPR/Cas9 (e.g., EBT-101) designed to excise the proviral DNA from the host genome (Molecular Therapy, 2020, doi:10.1016/j.ymthe.2020.06.029; Excision BioTherapeutics, 2022). These interventions aim to either deplete the reservoir or render it permanently inactive, representing the frontier of HIV cure research.

Other names

Integrated HIV-1 DNAHIV-1 latent reservoirHIV-1 DNA genomeIntegrated HIV-1 genome

Latency reversal (shock and kill), transcriptional silencing (block and lock), or direct genomic excision via gene editing technologies.