Restriction factors are potent, widely expressed, intracellular blocks to viral replication that are an important component of the innate immune response to viral infection. Through evolutionary pressure for both host survival and virus emergence, an evolutionary “arms race” has developed that drives continuous rounds of selection for beneficial mutations in restriction factor genes to avoid viral escape from these factors and virus adaptation to gain the ability to antagonize the restriction factors. The study of the evolution and function of restriction factors, including that of the host protein APOBEC3G and the viral protein Vif,  allowed us to discover the steps that led to the ancient origins of HIV in old world primates to chimpanzees and subsequently to humans. This work is being continued in the lab of Harmit Malik. 

We developed a technology for doing high throughput CRISPR/Cas screens for host factors that affect HIV replication. This technique, called HIV-CRISPR, is one where we simultaneously knock out large numbers of genes with libraries of guideRNAs and then trick the virus into revealing which knockouts improve or decrease virus replication.  We used this technique to define the host factors that HIV requires to replicate in T cells, and adapted this screening technique to identify pathways necessary for establishment and maintenance of HIV latency—a key step in HIV Cure research.  Data and visualization of all of our published CRISPR screens is available at https://www.crisprvirus.org/ .