The Infection Biology Unit is studying virus-host cell interactions and their contribution to viral spread and pathogenesis in the host.
One focus of our work is on activation of viruses by host cell proteases. We are investigating which proteases are usurped by influenza viruses and emerging viruses to ensure their activation and how activation can be inhibited. Since diverse viruses can depend on the same protease for activation, it is conceivable that inhibitors of these enzymes might exert broad antiviral activity, similar to broadband antibiotics, which are used to treat diverse bacterial infections. Our recent studies provided evidence that the cellular protease TMPRSS2 is essential for influenza virus spread in mice and primate respiratory epithelium, indicating thatTMPRSS2 is an attractive target for antiviral intervention. Therefore, our future work seeks to define the antiviral activity of TMPRSS2 inhibitors in non-human primates.
The interferon system constitutes the first barrier against virus infection. A second focus of our studies is on the question how antiviral effector proteins of the interferon system inhibit viral spread and how viruses counter their antiviral activity. To answer this question, we employ siRNA and CRISPR/Cas9 approaches, life cell imaging, viruses with reporter function and ex vivo cultures of primate organs. Moreover, we are conducting, jointly with colleagues at DPZ, genetic analyses in order to reveal whether polymorphisms in genes encoding antiviral effectors impact disease development.
Another goal of the Infection Biology Unit is the diagnostic of viral infections of non-human primates. Transmission of herpes B virus from macaques to humans and transmission of herpes B-related viruses between non-human primates can result in fatal disease. Therefore, the work of the Infection Biology Unit is focused on establishing herpes virus diagnostics. However, our mid-term goal is to develop diagnostic tests for a broader spectrum of viral infections, which impact animal health. In order to attain this goal, we have recently implemented chip-based diagnostic tests for antibody detection.
Zmora P., P. Molau-Blazejewska, S. Bertram, K. Walendy-Gnirß, I. Nehlmeier, A. Hartleib, AS. Moldenhauer, S. Konzok, S. Dehmel, K. Sewald, C. Brinkmann, C. Curths, S. Knauf, J. Gruber, K. Mätz-Rensing, F. Dahlmann, A. Braun, and S. Pöhlmann. Non-human primate orthologues of TMPRSS2 cleave and activate the influenza virus hemagglutinin. PLoS One. 2017 11;12(5).
Gerlach T., L. Hensen, T. Matrosovich, J. Bergmann, M. Winkler, C. Peteranderl, HD. Klenk, F. Weber, S. Herold, S. Pöhlmann, and M. Matrosovich. pH Optimum of Hemagglutinin-Mediated Membrane Fusion Determines Sensitivity of Influenza A Viruses to the Interferon-Induced Antiviral State and IFITMs. J Virol. 2017 12;91(11).
Pöhlmann S., A. Krüger, W. Hafezi, S. Schneider, J. Gruber, M. Winkler, and A. Kaul. Detection systems for antibody responses against herpes B virus. Primate Biol. 2017 4, 9-16.