Lynn Middle Dustin, Ph.D.Research Associate Professor
Laboratory of Virology and Infectious Disease
Dr. Dustin studies the mechanisms by which the hepatitus C virus (HCV) evades the adaptive immune response and how viral manipulation of lymphocytes during chronic infection can cause additional pathologies. HCV has chronically infected more than 120 million people worldwide, putting them at high risk of developing cirrhosis, hepatocellular carcinoma, and extrahepatic disease. In the developed world, HCV is the leading reason for liver transplantation. Increased understanding of how this pathogen interacts with host defenses and with candidate antiviral compounds could lead to badly needed antiviral therapies or a vaccine.
HCV accomplishes the goal of every pathogen: by evading the immune system, the virus often establishes a life-long infection, maximizing opportunities for transmission. Exactly how HCV eludes the immune system is not well understood. The apparent ability of HCV to influence B cell function has led to speculation that these cells may be permissive to infection; indeed an essential HCV entry factor, CD81, is expressed on the surface of B cells. Dr. Dustin’s studies, however, have found that HCV infection of lymphocytes is blocked at multiple steps. This suggests that B cells likely do not function as a reservoir of replicating virus, and Dr. Dustin is investigating other mechanisms by which HCV may modulate lymphocyte activity.
Some of the same characteristics that allow HCV to evade the immune system also mediate resistance to antiviral drugs. Rapid evolution of HCV genomes through the error-prone activity of the RNA-dependent RNA polymerase facilitates escape from antiviral compounds. Dr. Dustin’s current research is investigating the development of drug-resistance using a cell culture model of HCV replication. She hopes to understand the types of mutations that arise in the presence of inhibitors, and how these affect the fitness of the virus under different conditions.
Dr. Dustin received her bachelor's degree in biology from Boston University and her Ph.D. in immunology from Harvard University, where she was a National Science Foundation Predoctoral Fellow. She completed her postdoctoral training at Washington University in St. Louis, and became a faculty member at St. Louis University School of Medicine before joining The Rockefeller University in 2001.