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.