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.
Inhibition of lectin-dependent enhancement of Ebola virus entry into cells
The cellular lectins DC-SIGN and DC-SIGNR bind to N-glycans present on Ebola virus and other pathogens and can augment viral entry into cells. DC-SIGN/R exhibit high sequence similarity but differ in their spectrum of ligands. This study, led by Drs. Guo and Zhou, University of Leeds, UK, shows that quantum dots (QD) displaying a dense array of mono-/disaccharides allow to dissect the multivalent protein-glycan interactions underlying ligand binding to DC-SIGN/R. Moreover, the research demonstrates that QDs can be used to block augmentation of Ebola virus cell entry by DC-SIGN/R.
Guo et al. Dissecting Multivalent Lectin-Carbohydrate Recognition Using Polyvalent Multifunctional Glycan-Quantum Dots. J Am Chem Soc. 2017 Aug 30;139(34):11833-11844.
pH dependence of influenza A viruses is linked to interferon- and IFITM3-sensitivity
Influenza A viruses (IAV) fuse with target cells upon exposure to low pH and fusion is essential for IAV infection. Moreover, IAV infection can be blocked by interferon (IFN) and IFITM3, an IFN-inducible antiviral host cell protein. This study, led by the laboratory of Prof. Matrosovich at Philipps University Marburg, shows that the level of acidic pH required to trigger fusion also determines interferon- and IFITM-sensitivity of IAV. These finding suggest that IAV might evade the IFN response by adapting to high pH for membrane fusion.
Gerlach et al. 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).