Transcriptional regulation of HIV LTR and mechanism of HIV latency and reactivation

Anti-retroviral therapy for HIV typically suppresses the virus in patients' blood to undetectable levels, enabling people with the infection to live symptom-free. However, some T cells are latently infected by HIV and remain unaffected even by prolonged treatment. These latently infected cells and other lymphocytes pose the major barrier to eliminating HIV infection, and provide a latent reservoir for the virus to reactivate. Long-term anti-retroviral treatment can also cause HIV resistance to therapy in some patients. An alternate strategy is therefore needed to target the latently infected virus and ultimately cure AIDS. Dr. Jiguo Chen is researching how HIV-1 establishes latency and how it reactivates. He and other colleagues in the Sadowski lab have isolated and identified a complex of several transcription factors termed RBF-2 (Ras-responsive element binding factor), which binds to HIV long terminal repeat (HIV-1 LTR) and represses HIV-1 transcription during latency. He believes that this complex plays a role in establishing and maintaining latency. He is using several different experimental strategies to determine the role of RBF-2 and to learn how it works during latency and reactivation, so new drug therapies can be designed to clear HIV from patients' immune systems.