Viral reservoir (VR)

The viral reservoir refers to a population of long-lived, latently infected cells that harbor a virus in a dormant state, allowing it to persist indefinitely despite effective antiviral treatment and host immune responses (NIH, 2023). In the context of HIV-1, this reservoir primarily consists of resting memory CD4+ T cells that contain integrated proviral DNA that is transcriptionally silent (Nature Reviews Microbiology, 2019). These reservoirs are established very early during acute infection and are found in various anatomical sites, including the lymph nodes, gut-associated lymphoid tissue, and the central nervous system. Because current antiretroviral therapies (ART) only target actively replicating viruses, they are unable to eliminate the latent reservoir, which serves as the source for viral rebound if therapy is discontinued (The Lancet HIV, 2020). Therapeutic approaches currently under investigation aim to either purge the reservoir through 'shock and kill' methods using histone deacetylase (HDAC) inhibitors or reinforce viral latency through 'block and lock' strategies. Successfully targeting and eliminating the viral reservoir remains the most significant barrier to achieving a functional or sterilizing cure for chronic viral infections like HIV and Hepatitis B.

Other names

Latent viral reservoirHIV-1 reservoirProviral reservoirLatently infected cell populationAnatomical viral sanctuary

Strategies targeting the reservoir include 'shock and kill' (using latency-reversing agents to induce viral expression for immune clearance) and 'block and lock' (using inhibitors to permanently silence viral transcription and prevent rebound).