Evolution-based CRISPR Screen for Novel HIV-Host Interactions

Despite impressive advances in the treatment of HIV/AIDS over the past 30 years, there is much we do not understand about the HIV life-cycle. While it is well-known that HIV and related primate lentiviruses induce an aberrant DNA damage response (DDR) in infected cells, it remains unclear exactly how or why this occurs. Working from a curated list of 40 human genes associated with DDR, bearing markers of positive selection, and induced by interferon gamma signaling, we performed a CRISPR screen for genes that increased or decreased infectivity upon knockout in primary CD4+ T cells. The results were analyzed by one-sample T-test to identify putative susceptibility and antiviral genes. Subsequently, preliminary experiments were conducted to verify the results of the screen via overexpression and shRNA silencing experiments. This study has identified ESPL1, PALB2, and RBBP8 as potential susceptibility factors, and POLG, MUTYH, and BRIP1 as potential antiviral factors