Grant: Project Grant

Viral latency currently constitutes one of the most formidable obstacles to curing HIV infection. Combination antiretroviral therapy (cART) is extremely effective at suppressing HIV infection and replication, but fails to eliminate long-lived immune cells infected with a dormant or latent virus. Latent viruses can persist indefinitely inside a cell until reactivated in periods of stress or when a patient interrupts cART. Several cellular mechanisms have been identified that can partially explain how HIV becomes latent, but the complete scheme of latency inducing factors has not yet been defined. Our research has recently revealed that certain types of mutations caused by the viral polymerase and by host immune proteins called APOBEC3 can contribute to create mutated viruses with a predisposition to become latent, thereby highlighting a potential new mechanism for latency. The research we propose will explore how these mutations cause HIV to become latent and in some instances resist the effects of various latency-reversing agents (LRAs). Our research will help to better understand HIV latency, contribute to the design of a new platform for testing the next generation of LRAs, and identify prognostic mutations in the viral DNA that will help predict the effectiveness of latency-reversal therapies.