Abstract

HIV-1 has two subsets defined by coreceptor use, X4- and R5-tropic virus, with only R5-tropic virus observed clinically during the early stages of infection. Our preliminary work demonstrated that the human innate immune response is capable of restricting the replication of X4-tropic virus. We hypothesize that this occurs due to the human innate immune response reducing the rate of intra-host evolution and enabling the adaptive immune system to clear infection. To develop this as a therapeutic target, I will investigate the mechanisms that mediate restriction of X4-tropic virus by the innate immune system in CD4+ T cells, whether slowing viral evolution does indeed enhance adaptive immune clearance of HIV, and how X4- tropic virus emerges in late-stage AIDS. We expect that these efforts will identify novel therapeutic targets that can be leveraged to induce similar clearance of R5-tropic virus.