Seminar - Regulation of HIV latency
Division of Clinical Microbiology, Department of Laboratory Medicine present Thursday seminar:
"Regulation of HIV latency"
Peter Svensson, senior researcher
Department of Biosciences and Nutrition
Even under the best current treatment, an HIV-positive individual maintains a reservoir of latently infected cells. A challenge as to cure HIV lies in understanding and manipulating the transition between active and silent provirus. Active replication is under a positive feedback loop with the viral Tat protein, but long-lived latent cells are devoid of all viral proteins. Here we seek the initial appearance of Tat to spark the viral replication in latent cells. Using primary CD4+ T cells from several donors, cells were transduced with HIV-1 and we followed the maturation process of the proviral chromatin. We have methodically mapped a panel of chromatin marks as well as RNA PolII occupancy and transcription. Whereas, over time, the proviral latency reversal became less susceptible to induction, “spontaneous” latency reversal remained active. We isolated a mature mRNA resulting from an intragenic promoter in un-induced cells. This transcript encodes Tat and thus is expected to able to initiate the canonical LTR promoter resulting in productive HIV replication. These results may explain how HIV latency reversal can occur in the absence of viral proteins, such as is the case in long-lived memory T cells.