The Infection Biology Unit is studying virus-host cell interactions and their contribution to viral spread and pathogenesis in the host.
Many viruses that cause severe diseases in primates are activated by host cell proteases. The responsible enzymes are potential targets for novel antivirals and are in the focus of our research efforts. Our recent studies provide evidence that the cellular protease TMPRSS2 is essential for influenza virus spread in mice and primate respiratory epithelium, and show that TMPRSS2 is used by other viruses to ensure their activation. Therefore, TMPRSS2-inhibitors might exert broad antiviral activity, similar to broadband antibiotics used to treat diverse bacterial infections.
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 Infection Biology Unit is developing herpes virus diagnostics. In addition, we offer diagnostic tests for several other viral infections, including chip-based antibody detection suitable for screening of non-human primate colonies.
Recent publications summarized in three sentences
Enveloped viruses depend on activation by host cell proteases for acquisition of infectivity. Zmora and colleagues show that the cellular serine protease TMPRSS11A activates influenza A viruses and MERS coronavirus. Moreover, they provide evidence that TMPRSS11A is not blocked by the cellular protease inhibitor HAI-I.
Zmora et al, TMPRSS11A activates the influenza A virus hemagglutinin and the MERS coronavirus spike protein and is insensitive against blockade by HAI-1. J Biol Chem. 2018 Jul 5. pii: jbc.RA118.001273.
Hoffmann and Pöhlmann comment on the finding that influenza A viruses use a cellular sialylated Ca++ channel as receptor for host cell entry.
The Ebola virus glycoprotein antagonizes the antiviral host cell factor tetherin. González-Hernández and colleagues show that a GXXXA motif within the transmembrane domain of the Ebola virus glycoprotein is required for inhibiton of tetherin. This finding should help to define the contribution of tetherin antagonism to Ebola virus spread and pathogenesis in the host.
VSV-G antagonizes tetherin in transfected cells
We show that the G protein of vesicular stomatitis virus (VSV-G) blocks the antiviral host cell factor tetherin, at least upon directed expression. However, our study failed to provide evidence that VSV-G-mediated tetherin antagonism is operative in infected cells.
Brinkmann et al. The glycoprotein of vesicular stomatitis virus promotes release of virus-like particles from tetherin-positive cells. PLoS One. 2017 Dec 7;12(12):e0189073