Our group is interested in illuminating the mechanisms behind the various sophisticated immune evasion strategies of cytomegaloviruses (CMV). These viral strategies are a result of an evolutionary arms race between pathogen and host, which lead to a stalemate situation where host and virus can co-exist. However, once this balance is broken by immunodefiniencies (pregnancy, organ transplantation, disease) CMV infection can cause severe disease. Understanding viral evasion strategies not only allows for the development of antiviral strategies, but also enables us to further elucidate cellular responses to viral infection. To do so, we are establishing novel tools to examine cellular effector functions which help us to understand the intricate interplay between CMV and its host.
The best way to counteract can be to copy. In the case of CMV this is true for its strategy to evade host immune responses triggered by antibody recognition via Fc-receptors.
One of the most powerful reactions of the immune system towards pathogen invasion is the generation of specific antibodies. This may not only directly attack the unwanted intruder but also works as a link to trigger or strengthen various arms of the immune system such as antibody dependent cellular cytotoxicity (ADCC) to kill virus infected cells that are decorated with virus specific antibodies. To specifically counteract such an attack on virus-infected cells which is mediated by Fc-receptors, the CMV genome encodes its own Fc-receptors.
Our main research goal is to characterize viral Fc-receptors and learn more about Fc-receptor activation in general.
How many inhibitors does it take to persistently cope with cytotoxic lymphocytes?
For a virus it is a huge act of balance to escape CD8+ T-cell recognition without exposing itself to NK cells. To cope with these two fronts of immune attack the human cytomegalovirus (HCMV) encodes for several inhibitors of classical and non-classical MHC class I molecules. Our main research interest concerns HCMV manipulation of MHC class I antigen presentation: what are the detailed mechanisms behind this and how will it impact immune cell recognition?
Cytomegaloviruses (CMVs) are DNA viruses with large and complicated genomes. Genetic manipulation of CMVs including the construction of recombinant or mutant viruses is extremely difficult. However, during the last two decades bacterial artificial chromosomes (BACs) have become very powerful tools for genetic engineering of CMV allowing for new genetic approaches to better understand the biology and pathogenesis of these viruses. We developed new methods for genetic analysis of essential viral genes and applied them to investigate CMV morphogenesis. This work aims at identifying new drug targets for antiviral therapy. We are also exploring recombinant CMVs as viral vectors, focusing on development of recombinant vaccines.