CeMM Principal Investigator

Andreas Bergthaler
Viral Pathogenesis and Antiviral Immune Responses

Our group is interested in how our immune systems respond to viral infections. We integrate well-defined mouse infection models with molecular techniques of immunology, virology and systems biology to gain mechanistic insights into viral pathogenesis and the multilayered antiviral immune response. The ultimate goal is a better understanding of how viruses cause disease, which will help to identify novel therapeutic avenues for better treatment of infectious diseases.

Interplay between persistent viruses and the host immune system

Persistent viral infections affect millions of people worldwide, yet treatment options remain limited due to a lack of understanding of the molecular mechanisms used by the viruses to cause disease. Many of these mechanisms involve direct interactions with the host immune system.

To study how viruses cause disease we employ a prototypic infection model with a small mouse virus, lymphocytic choriomeningitis virus (LCMV). By targeted genetic perturbations of the virus as well as the host we are investigating how the virus interacts with the host immune system to initiate and sustain infections over extended time periods. We are particularly interested in the role of the host antiviral innate immune response, as well as CD8 T and B cell responses to chronic viral infections.

Pathogenesis of virus-induced immunopathologies

Viral infections can be associated with other diseases such as hepatitis or pneumonia leading to severe organ damage. Viruses may also suppress the immune system thereby facilitating detrimental superinfections by bacteria or other viruses. To help us study the mechanisms underlying these phenomena, we use different infection models and have set up collaborations with clinical groups at the adjacent Medical University of Vienna. This enables us to focus on the pathogenesis of virus-induced immunopathologies that are of relevance to patients.

Biosketch

Andreas Bergthaler studied Veterinary Medicine in Vienna. He undertook graduate and postgraduate research with Hans Hengartner and Rolf Zinkernagel at the University of Zurich and ETH Zurich followed by postdoctoral positions with Daniel Pinschewer at the University of Geneva and with Alan Aderem at the Institute for Systems Biology in Seattle. He joined CeMM in 2011.

Selected Papers

Bhattacharya A, et al. Superoxide dismutase 1 protects from type I interferon-driven oxidative damage in viral hepatitis. Immunity 2015 Nov 17; 43(5):974–986 (abstract)

Johnson S, et al. Protective Efficacy of Individual CD8+ T Cell Specificities in Chronic Viral Infection. J Immunol. 2015 Feb 15; 194(4):1755-62. doi: 10.4049/jimmunol.1401771. Epub 2015 Jan 7 (abstract)

Schliehe C. et al. The methyltransferase Setdb2 mediates virus-induced susceptibility to bacterial superinfection. Nature Immunology 2015 Jan; 16(1):67-74. doi: 10.1038/ni.3046. Epub 2014 Nov 24. (abstract)

Litvak V, et al. A FOXO3-IRF7 gene regulatory circuit limits inflammatory sequelae of antiviral  responses. Nature 2012 Oct 18; 490(7420):421-5. doi: 10.1038/nature11428. Epub 2012 Sep 16. (abstract)

Bergthaler A, et al. Viral replicative capacity is the primary determinant of lymphocytic choriomeningitis virus persistence and immunosuppression.Proc Natl Acad Sci U S A. 2010 Dec 14; 107(50):21641-6. Epub 2010 Nov 22. (abstract)

Hegazy AN, et al. Interferons direct Th2 cell reprogramming to generate a stable GATA-3(+)T-bet(+) cell subset with combined Th2 and Th1 cell functions. Immunity 2010 Jan 29; 32(1):116-28. Epub 2010 Jan 14. (abstract)

Bergthaler A, et al. Impaired antibody response causes persistence of
prototypic T cell-contained virus. PLoS Biol.2009 Apr 7; 7(4):e1000080 (abstract)