Viral-host interactomes map the complex architecture of an evolved arms race during host-cell invasion. mRNA and protein interactomes have revealed elaborate targeting schemes, yet evidence for genetic coupling, resulting in the co-regulation of promoters, remains elusive. I will present a genetic to single-cell study from our lab using computational and experimental approaches on viral-host interactomes of human immunodeficiency virus (HIV), and its ability to genetically couple and co-regulate itself with endogenous pathways throughout the human genome. We find that viral-host co-evolution is imprinted within promoter gene sequence, i.e. prior to transcript or protein interactions. Discovered co-regulation of HIV and a major chemokine receptor facilitates migration of infected cells. Upon infection, HIV can either actively replicate or remain dormant. Cells producing virus pose a risk for reinitiating infection within niches inaccessible to drug treatments, and tuning viral control of migration and reactivation improves strategies to eliminate latent HIV. Viral-host genetic coupling establishes a novel mechanism for synchronizing transcription and guiding potential therapies.
From: “Genetic coupling of viral-host gene expression presents migratory challenges in HIV therapies” K. Bohn-Wippert, E. N. Tevonian, M. R. Megaridis, and R. D. Dar, Nat. Commun. (in press, 2017)