Fig. 1. RNA viruses, including HCV, are sensed as “non-self” in the infected cell by pattern recognition receptors to activate the antiviral innate immune response. We study the cell biology the regulates this activation and how viruses evade innate immunity.
Studying the RNA biology, cell biology, and immunology of RNA virus infection
Our goal is to understand the molecular mechanisms that coordinate innate immunity to hepatitis C virus (HCV) and other RNA viruses, as well as to understand how viruses evade these host innate immune defenses during infection. HCV is a major human pathogen that is a leading cause of liver disease and liver cancer and infects nearly 200 million of people worldwide. The virus maintains a persistent course of infection in around 80% of those infected in part due to its ability to control antiviral innate immune defenses through the actions of the HCV NS3/4A protease. While HCV infection is sensed in hepatocytes by RIG-I, a cytosolic pathogen recognition receptor that engages pattern-associated molecular patterns in viral RNA to activate downstream signaling of innate immunity through the signaling adaptor protein MAVS, the HCV NS3/4A protease cleaves the MAVS protein releasing it from intracellular membranes to prevent this signaling ultimately leading to viral persistence (Fig. 1).
Our laboratory focuses on identifying and characterizing the key host and viral factors, as well as metabolic processes, which drive and regulate innate immunity during infection with HCV and other RNA viruses that are sensed by the RIG-I pathway. In particular, we are interested in the role that intracellular membranes play in organizing innate immune signaling platforms during RNA virus infection (Fig. 2). We are also studying how the HCV NS3/4A protein hijacks host cell components on intracellular membranes to turn off innate immune signaling during HCV infection. We use an interdisciplinary approach to study antiviral innate immunity, combining techniques from cell biology, virology, biochemistry, and systems biology to reveal the viral and host strategies that coordinate and regulate innate immunity, with the ultimate goal of developing new immunomodulatory strategies for virus treatment and prevention.
Sound interesting? Contact Dr. Horner to discuss joining the lab.