The main obstacle to curing HIV is the reservoir of latent but replication-competent proviruses inside the CD4+ T cells that orchestrate the immune response.
This study group examined subpopulations of CD4+ T cells from 10 HIV patients on antiretroviral therapy. They examined the hypothesis that certain CD4+ memory T cell subsets habour latent proviruses in a deeper state of latency, allowing the cell to proliferate without producing viral proteins, thus allowing the virus to evade immune detection. A multiple stimulation viral outgrowth assay to culture CD4+ T cells revealed a low inducibility of HIV-1 proviruses under experimental conditions.
“Latency may initially be due to the lack of key host factors needed for HIV gene expression,” said Dr Robert F. Siliciano, the research leader. Epigenetic changes may contribute to silencing HIV gene expression, driving HIV into a deeper state of latency.
Those nonadherent to their antiretroviral medication risk a bombardment of newly replicating viruses reactivated from the latent pool of proviruses.
Proliferation of HIV-infected CD4+ cells is a major factor in the generation and persistence of this latent reservoir.
Intact HIV-1 proviruses are distributed among different memory CD4+ T cell subsets.
Central memory T cells, transitional memory T cells and effector memory T cells. “Latency occurs when some activated T cells become infected as they are reverting back to a resting state in which host factors needed for HIV gene expression are no longer available," said Dr Robert F. Siliciano.