Current EIDIS projects are focused on virus-host cell interactions and their role in viral spread and pathogenesis:
Prerna Arora and Najat Bdeir are investigating how defective interfering particles (DIPs) can be exploited for influenza therapy and prevention. The project is based on the discovery that genomic segments of influenza A viruses (IAV) harboring deletions can arise in the context of natural infection and can induce formation of DIPs and blockade of viral replication. The goal of the work of Prerna Arora and Najat Bdeir is to generate tools for efficient production of DIPs, to identify DIPs with potent antiviral activity and to obtain insights into the molecular processes underlying inhibition of IAV infection by DIPs
Hannah Kleine-Weber is studying host cell interactions of the Middle East Respiratory syndrome coronavirus (MERS-CoV). At present, MERS-CoV spread between humans is inefficient and it is unknown which adaptive changes are required for the virus to become readily transmissible and thus to acquire pandemic potential. The work of Hannah Kleine-Weber will investigate the concept that MERS-CoV adaptation to efficient use of the cellular protease TMPRSS2, which activates the viral spike protein, might be a perquisite for robust and sustained human-human transmission and might thus serve as an indicator of the pandemic potential of newly emerging MERS-CoV variants.
Mariana González Hernández is interested in host cell interactions of Ebola virus. She is studying how the glycoprotein (GP) of ebolaviruses counteract the interferon-induced antiviral host cell factor tetherin and will clarify whether tetherin counteraction is important for viral spread in target cells. Moreover, Mariana González Hernández will determine whether activation of the viral GP by the cellular cysteine proteases cathepsin B and L is required for viral entry into primary target cells and organs ex vivo.
Teresa Plegge is investigating how the glycoproteins of emerging bunyaviruses are activated by host cell proteases. Her recent work is focused on the contribution of signal peptide peptidase and SKI-1 to activation of bunyaviruses and other emerging viruses as well as on strategies to interfere with these processes.
Anna Großkopf is studying how Kaposi’s sarcoma-associated herpesvirus (KSHV) and the related rhesus monkey rhadinovirus (RRV) interact with host cell receptors. She has identified specific residues in each virus’ glycoproteins that are critical for binding cellular Eph family receptor tyrosine kinases and has generated virus mutants that can no longer interact with these molecules. Using these mutants, she has characterized alternative cellular receptors for RRV and is currently looking for additional cellular factors that govern infection by KSHV.
Candice D’Costa is analyzing the effect of interferon-induced transmembrane proteins (IFITMs) on infection by the Kaposi’s sarcoma-associated herpesvirus (KSHV) and the related rhesus monkey rhadinovirus (RRV). IFITMs restrict cellular entry of a broad range of enveloped viruses that infect cells through an endocytotic pathway. KSHV and RRV, unlike many other herpesviruses, enter cells predominantly through endocytosis. We therefore hypothesize that IFITMs may affect infection by KSHV and RRV under some circumstances. Looking also at host factors that may enhance infection, Candice analyzes the effect of calcium channels on establishment of KSHV/RRV infection.