Dynamics of viral infection

The project investigates the fundamental aspects of host/pathogen interactions, specifically the interplay between viral replication and innate immune response at the individual cell level. It focuses on cytosolic viral sensors (CyVSP) like PKR, RIG-I, and MDA5, which detect viral RNA. The research discovered that successful viral replication requires surpassing a 'virus input threshold for replication' (VITREP), which activates negative feedback regulators to suppress innate signaling. Experiments using multiple viral infections in diverse human cell types showed that only supra-unitary levels of viral RNA trigger these suppressors, independent of viral protein synthesis or replication. The findings were supported by an adaptive kinetic proofreading model and quantitative measurements, identifying VITREP as a conserved and tunable checkpoint in viral pathogenesis.