MOLECULAR MECHANISMS OF HIV-1 LATENCY

Advances in the treatment of HIV-1 infection with§highly active anti-retroviral therapy (HAART) have§greatly reduced mortality and changed this fatal§infection into a chronic disease for many. HAART can§reduce viremia to below the clinical limit of§detection. However, eradication of the infection has§not been achieved. HIV-1 can establish latent§infection in a small pool of resting memory T cells§in which the provirus is stably integrated into the§host genome but not producing viral proteins. This§state of latency allows HIV-1 to evade immune§responses and antiretroviral drugs. Upon cellular§activation, replication-competent viruses can be§quickly released from the latent reservoir to§rekindle the infection. Because of its extremely slow§decay rate, the latent reservoir is a major barrier§to curing HIV-1 infection. Dr. Han s dissertation§explored the molecular mechanisms underlying this§unique nature of the infection in resting CD4+ T§cells, starting from the first in vivo analysis of§integration sites in resting CD4+ T cells to the§novel discovery of the bidirectional regulation on§integrated HIV-1 by the host gene transcriptional§read-through.