von Jil Alexandra Haase ; Abarna Baheerathan ; Xin Zhang ; Rebecca Menhua Fu ; Maximilian K. Nocke ; Charlotte Caroline Decker ; Viet Loan Dao Thi ; Daniel Matthias Todt ; Johan Neyts ; Suzanne J.F. Kaptein ; Eike Steinmann ; Volker Kinast
Background: HEV is a positive-sense, single-stranded RNA virus of the Hepeviridae family. Although HEV accounts for more than 3 million symptomatic cases of viral hepatitis per year, specific anti-HEV therapy and knowledge about HEV pathogenesis are scarce. Methods: To gain a deeper understanding of the HEV infectious cycle and guide the development of novel antiviral strategies, we here used an RNAi mini screen targeting a selection of kinases, including mitogen-activated protein kinases, receptor tyrosine kinases, and Src-family kinases. Further, we used state-of-the-art HEV infection models, including primary human hepatocytes and athymic nude rats. Results: Upon knockdown of the Src-family kinase Yes1, a significant reduction of HEV susceptibility could be observed, suggesting an important role of Yes1 in the HEV infectious cycle. Selective inhibition of Yes1 kinase activity resulted in significant inhibition of HEV infection in hepatoma cells and primary human hepatocytes, as well as in a rat HEV in vivo model system. Subsequent analysis of Y1KI during the HEV infectious life cycle indicated a role of Yes1 kinase activity in the early onset of HEV infection. Conclusions: We identified the dependence of HEV on Yes1 signaling, which may contribute to the so far scarce knowledge of HEV’s pathogenesis in the future. Moreover, we provide Y1KI as a novel antiviral drug candidate specifically targeting an HEV host factor.
Hepatology communications [Alphen aan den Rijn] : Wolters Kluwer Health, 2017 8(2024), 11 vom: Nov., Artikel-ID e0553, Seite 1-11 Online-Ressource
von Jil Alexandra Schrader ; Thomas L. Burkard ; Yannick Brüggemann ; André Gömer ; Toni L. Meister ; Rebecca Menhua Fu ; Ann-Kathrin Mehnert ; Viet Loan Dao Thi ; Patrick Behrendt ; David Durantel ; Ruth Broering ; Florian W. R. Vondran ; Daniel Todt ; Volker Kinast ; Eike Steinmann
Being the most common cause of acute viral hepatitis with >20 million cases per year and 70,000 deaths annually, HEV presents a long-neglected and underinvestigated health burden. Although the entry process of viral particles is an attractive target for pharmacological intervention, druggable host factors to restrict HEV entry have not been identified so far. ...
Hepatology [Alphen aan den Rijn] : Wolters Kluwer Health, 1981 77(2023), 6 vom: Juni, Seite 2104-2117 Online-Ressource
von Volker Kinast ; Ioana Andreica ; Gerrit Ahrenstorf ; André Philipp Gömer ; Carina Elsner ; Sarah Schlienkamp ; Jil Alexandra Schrader ; Mara Klöhn ; Rainer G. Ulrich ; Ruth Broering ; Axel Hamprecht
von Dimas F. Praditya ; Mara Klöhn ; Yannick Brüggemann ; Lauren E. Brown ; John A. Jr. Porco ; Wenhan Zhang ; Volker Kinast ; Andreas Kirschning ; Florian W.R. Vondran ; Daniel Todt ; Eike Steinmann
