CeMM Principal Investigator

Andreas Bergthaler
Viral Pathogenesis and Antiviral Immune Responses

Our group is interested in how inflammatory processes are regulated and how the immune system responds to viral infections. We dissect well-defined mouse infection models and cell culture systems 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 molecular understanding of pathogen control and how tissue damage develop. This may lead to the identification of novel therapeutic avenues to ameliorate and/or prevent immunopathologies in infectious and inflammatory diseases.

Systemic crosstalk between metabolism and inflammation

Inflammatory processes are tightly linked to metabolic pathways including secreted metabolites and cytokines. Yet, comparatively little is known about the metabolic-inflammatory crosstalk at whole organism level. We aim to characterize and delineate these interconnected pathophysiological processes by using various models for acute and chronic viral infections. A primary focus rests on the liver as the central organ for metabolism and a hotspot for receiving, processing and distributing local and systemic signals. Systems-level and hypothesis-driven approaches are integrated to identify novel regulatory nodes between metabolism and inflammation. This framework of systemic immunometabolism aims at a deeper understanding of inflammation in the context of viral infections on an organ and organism-level. 

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 the lymphocytic choriomeningitis virus, which represents a well-defined benchmark model of viral persistence. Targeted perturbations of the virus as well as the host enable us to investigate how viruses interact with the immune system and sustain infections over extended time periods. We are particularly interested in the role of the antiviral innate immune response, organ-specific CD8 T responses and evolutionary viral evasion strategies during chronic infection.

Pathogenesis of virus-induced immunopathologies

Viral infections are associated with co-morbidities 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. We investigate the underlying mechanisms and the complex molecular interactions of pathogens and their host in various infection models including influenza virus. We thereby expect to unveil critical disease-driving processes and molecules which may be amenable for targeted therapeutic interventions.

Molecular basis of transmissible cancers 

Cancer cells are generally not thought to be transmissible between different individuals. Yet, there are rare examples of horizontally transmissible cancers in the animal kingdom including in dogs, mollusks and Tasmanian devils. These cancers populate an intriguing conceptual space between cancer and infectious diseases. We investigate the molecular wiring of devil facial tumor disease (DFTD) of Tasmanian devils and the underlying mechanisms that drive cancer growth while preventing the immune rejection of transmitted cancer cells. We are also interested in pharmacological targeting of DFTD to contribute to the ongoing conservation efforts to prevent the extinction of this marsupial species. On a cross-disciplinary level we study both common and unique features of DFTD compared to infectious diseases and malignant diseases including metastasizing cancer.

Biosketch

Andreas Bergthaler studied veterinary medicine in Vienna. He undertook graduate and postgraduate research with Hans Hengartner and Nobel Laureate 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 is recipient of an ERC Starting Grant and several awards including the Löffler-Frosch-Prize of the Society of Virology (2016), the Georges-Köhler Prize of the German Society for Immunology (2016), the Seymour and Vivian Milstein Young Investigator Award of the International Cytokine and Interferon Society (2016) and the Austrian Infection Research Prize of the Austrian Society for Infectious Diseases and Tropical Medicine (2017). Andreas Bergthaler co-founded the clinical-stage immunotherapy company Hookipa Pharma. He joined CeMM in 2011.

Selected Papers

Kosack L, et al.  The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor Disease. Cancer Cell 2019 Jan 14. doi: 10.1016/j.ccell.2018.11.018 (abstract)

Khamina K , et al. Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein. PLoS Pathogens 13(12): e1006758; 2017. (abstract)

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)

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

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)