Ron Levy: epistasis and drug resistance in HIV

In our first episode of the National Science Foundation-sponsored EpistasisNet podcast, Jeffrey Townsend interviews Ron Levy of Temple University about his recent research article published in eLife, on epistasis and the entrenchment of drug resistance in HIV-1 subtype B. They talk about how he came to become engaged in this research direction, and how resistance to HIV arises as the result of primary mutations whose individual effects on viral fitness depend on the entire genetic background—a phenomenon called ‘epistasis’. They discuss the co-evolutionary (Potts) Hamiltonian models he uses to provide insight into epistasis involving many simultaneous mutations. Levy's research provides the first confirmation of this widespread epistasis in all three HIV drug-target proteins: the HIV protease, reverse transcriptase, and integrase.