Institute of Virology

Research Topics

Our lab is interested in the receptor-mediated interaction between viruses and the host, with a focus on host immunology. Current projects deal with antibody-mediated immunity against herpesviruses, antibody-mediated dissemination of viruses in the host and links between autoimmunity and viral infections.

1. Human Cytomegalovirus Immune Evasion and Congenital Infection

Human cytomegalovirus (HCMV) is one of the eight known human herpesviruses. It causes a particularly high disease burden in congenitally infected newborns, often leading to severe physical or sensorineural defects. One major reason for the success of HCMV in establishing life-long infection is its ability to withstand humoral immunity, particularly neutralizing IgG antibodies. Consequently, there is no vaccine available. Antiviral therapy against HCMV disease is restricted to few antiviral agents fraught with severe side effects including teratogenic damage and emergence of virus resistance. As they are not applicable in some clinical settings including pregnancy, vulnerable patient groups will greatly benefit from alternative intervention strategies with fewer risks. We are interested in solving the molecular mechanisms driving congenital HCMV infection and aim to identify viral targets for novel intervention and prevention strategies.

2. Antibody Immune Complexes in Autoimmunity and Infectious Diseases

Circulating soluble IgG immune complexes (sICs) are major culprits of systemic and local inflammation in certain autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). We recently developed a cell-based reporter assay, which enables the detection and characterization of sICs with unparalleled sensitivity in a variety of clinical samples and antibody preparations. Using this assay on SARS-CoV2 infected individuals, we were also able to uncover the existence of sICs in severely diseased COVID-19 patients. In doing so, we identified a completely novel mechanism in viral immunopathology and described a missing link that explains the uncanny similarities between severe COVID-19 and autoimmune diseases such as SLE. We are interested in exploring the existence of sICs in other infectious and autoimmune diseases and aim to reveal the exact composition of sICs to enable efficient sIC removal, ultimately alleviating systemic inflammation driven by the humoral immune response.

3. Poxvirus Evasion from Antibodies

Poxviruses secret an array of cytokine receptor mimics, which help them to evade a cellular immune response. We recently found out that one of these factors encoded by cowpoxvirus (CPXV), a virus that can cause human disease and uses rodents as a reservoir host, is able to interfere with antibody-mediated immunity as well. The protein CPXV-14 can actively inhibit activation of mouse immune receptors recognizing IgG antibodies. This in turn protects the virus from immune control by antibodies, effectively making it a virulence factor. We are interested in the identification of such factors in other poxviruses to learn about the impact of such immuno-modulators regarding poxvirus host range and virulence and potentially find new ways to protect humans from disease.