Non-induced HIV-1 provirus in latent reservoirs: a critical but neglected threat to HIV-1 eradication
Despite effective combination antiretroviral therapy (cART), human immunodeficiency virus-1 (HIV-1) persists in a latent form in resting CD4+ T cells as the main barrier to eradication. Reactivation of HIV gene expression in latently infected cells while patients are on cART is the currently favored approach to cure HIV infection.
The number of latently infected cells that can be induced to produce virus (~1 in 1,000,000 cells) in a single round of in vitro stimulation is much lower than the total number of resting CD4+ T cells containing HIV-1 DNA (~1 in 10,000 cells). These non-induced proviruses may represent an additional barrier to eradication. The main goal of my research is to understand whether these non-induced proviruses are a clinical threat that requires different or prolonged reactivation therapy, or whether they are defective and therefore unable to rekindle new rounds of viral replication. We hypothesize that a significant proportion of the proviruses that are non-induced in vitro are actually REPLICATION-COMPETENT. Characterization of the non-induced proviruses and comparison with autologous replication-competent viruses will provide insights into HIV-1 eradication strategies. Individual clones of full-length proviral genomes are reconstructed to characterize the mechanisms of latency, including viral factors, epigenetic impact and cytotoxic T cell response.