The Role of Ion Channels in HIV Pathogenesis
In spite of thirty years of study, how HIV kills T cells, especially bystander T cells, remains a mystery that has only recently begun to be unraveled. We performed RNA-Seq experiments in which we examined the effect of the HIV transactivating protein Tat on cellular genes. Strikingly, treatment with Tat resulted in massive increases in the expression of multiple ion channels, including those that transport both potassium and sodium. The increases in expression were confirmed using qRT-PCR, and were seen not only with Tat treatment but also with HIV infection itself. These effects on ion channels might contribute to HIV pathogenesis in several key ways: (1) Cell death; (2) Enhanced viral replication; and (3) Neurological complications of AIDS. Therefore, in this proposal we will examine in molecular detail the effect of Tat and HIV on ion channels and the subsequent effects on HIV replication and cell death.