TY - JOUR T1 - LY6E impairs coronavirus fusion and confers immune control of viral disease JF - bioRxiv DO - 10.1101/2020.03.05.979260 SP - 2020.03.05.979260 AU - Stephanie Pfaender AU - Katrina B. Mar AU - Eleftherios Michailidis AU - Annika Kratzel AU - Dagny Hirt AU - Philip V’kovski AU - Wenchun Fan AU - Nadine Ebert AU - Hanspeter Stalder AU - Hannah Kleine-Weber AU - Markus Hoffmann AU - H. Heinrich Hoffmann AU - Mohsan Saeed AU - Ronald Dijkman AU - Eike Steinmann AU - Mary Wight-Carter AU - Natasha W. Hanners AU - Stefan Pöhlmann AU - Tom Gallagher AU - Daniel Todt AU - Gert Zimmer AU - Charles M. Rice AU - John W. Schoggins AU - Volker Thiel Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/03/07/2020.03.05.979260.abstract N2 - Zoonotic coronaviruses (CoVs) are significant threats to global health, as exemplified by the recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1. Host immune responses to CoV are complex and regulated in part through antiviral interferons. However, the interferon-stimulated gene products that inhibit CoV are not well characterized2. Here, we show that interferon-inducible lymphocyte antigen 6 complex, locus E (LY6E) potently restricts cellular infection by multiple CoVs, including SARS-CoV, SARS-CoV-2, and Middle East respiratory syndrome coronavirus (MERS-CoV). Mechanistic studies revealed that LY6E inhibits CoV entry into cells by interfering with spike protein-mediated membrane fusion. Importantly, mice lacking Ly6e in hematopoietic cells were highly susceptible to murine CoV infection. Exacerbated viral pathogenesis in Ly6e knockout mice was accompanied by loss of hepatic and splenic immune cells and reduction in global antiviral gene pathways. Accordingly, we found that Ly6e directly protects primary B cells and dendritic cells from murine CoV infection. Our results demonstrate that LY6E is a critical antiviral immune effector that controls CoV infection and pathogenesis. These findings advance our understanding of immune-mediated control of CoV in vitro and in vivo, knowledge that could help inform strategies to combat infection by emerging CoV. ER -