Dustin, L Group | Viral Infection and Immunity

The long-term goal of our research is to dissect the interplay between persisting viral infections and the immune system, in order to devise new strategies to combat chronic infection. We study both innate and adaptive immune mechanisms. Our current research focuses on hepatitis C virus (HCV), which affects more than 130 million people worldwide.

Antibody responses to HCV are delayed and inefficient, and patients with chronic HCV infection are at increased risk of the B cell disorders mixed cryoglobulinemia and B cell non-Hodgkin lymphoma. We seek to understand how HCV infection contributes to the pathogenesis of mixed cryoglobulinemia, to define the repertoire of HCV-specific antibodies, and to learn how HCV-specific and pathogenic B cell responses influence cellular immunity to HCV. These studies are performed using clinical specimens and in collaboration with clinicians.

Another goal of our work is to learn how innate host defenses control HCV and other viruses. It is known that HCV can antagonize an infected cell’s virus recognition and antiviral machinery. We have demonstrated that primary liver cells acutely infected with HCV express λambda interferons and a number of interferon-stimulated genes, including cytokines and chemokines. Further work has shown that very low levels of the induced cytokines can work together to mediate potent antiviral activities against HCV and other viruses. The mechanisms behind such synergistic interactions between interferons and inflammatory cytokines are being studied with molecular biological, virological and cell biological tools.