Establishment of well-differentiated camelid airway cultures to study Middle East respiratory syndrome coronavirus

建立分化良好的骆驼科动物呼吸道培养物以研究中东呼吸综合征冠状病毒

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作者:Mitra Gultom #, Annika Kratzel #, Jasmine Portmann, Hanspeter Stalder, Astrid Chanfon Bätzner, Hans Gantenbein, Corinne Gurtner, Nadine Ebert, Hans Henrik Gad, Rune Hartmann, Horst Posthaus, Patrik Zanolari, Stephanie Pfaender, Volker Thiel, Ronald Dijkman

Abstract

In 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in Saudi Arabia and was mostly associated with severe respiratory illness in humans. Dromedary camels are the zoonotic reservoir for MERS-CoV. To investigate the biology of MERS-CoV in camelids, we developed a well-differentiated airway epithelial cell (AEC) culture model for Llama glama and Camelus bactrianus. Histological characterization revealed progressive epithelial cellular differentiation with well-resemblance to autologous ex vivo tissues. We demonstrate that MERS-CoV displays a divergent cell tropism and replication kinetics profile in both AEC models. Furthermore, we observed that in the camelid AEC models MERS-CoV replication can be inhibited by both type I and III interferons (IFNs). In conclusion, we successfully established camelid AEC cultures that recapitulate the in vivo airway epithelium and reflect MERS-CoV infection in vivo. In combination with human AEC cultures, this system allows detailed characterization of the molecular basis of MERS-CoV cross-species transmission in respiratory epithelium.

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