The overall goal of our laboratory is to obtain new insights into the host-virus interaction in HIV infection, and translate discoveries in molecular biology and virology to the clinic to lead to interventions that could eradicate HIV infection. A subpopulation of HIV-infected lymphocytes is able to avoid viral or immune cytolysis and return to the resting state. While this latent reservoir of HIV infection is a significant clinical problem, the molecular mechanisms that underlie it are enigmatic. We have found that cellular transcription factors widely distributed in lymphocytes can remodel chromatin and maintain quiescence of the HIV genome in resting CD4+ lymphocytes. Further studies are underway to understand how the host chromatin environment regulates HIV expression. The discovery of specific molecular mechanisms that selectively maintain HIV proviral quiescence presents the opportunity to disrupt persistence of HIV in CD4+ T cells, one of the most daunting obstacles to the clearance of retroviral infection. Clinical and animal model experiments have begun with the aim of depleting the pool of persistent, replication-competent provirus in the setting of potent antiretroviral therapy. It is hoped that the interruption of HIV latency will ultimately lead to therapies capable of eradicating HIV infection.