TY - JOUR
T1 - LY6E impairs coronavirus fusion and confers immune control of viral disease
AU - Pfaender, Stephanie
AU - Mar, Katrina B.
AU - Michailidis, Eleftherios
AU - Kratzel, Annika
AU - Boys, Ian N.
AU - V’kovski, Philip
AU - Fan, Wenchun
AU - Kelly, Jenna N.
AU - Hirt, Dagny
AU - Ebert, Nadine
AU - Stalder, Hanspeter
AU - Kleine-Weber, Hannah
AU - Hoffmann, Markus
AU - Hoffmann, Hans Heinrich
AU - Saeed, Mohsan
AU - Dijkman, Ronald
AU - Steinmann, Eike
AU - Wight-Carter, Mary
AU - McDougal, Matthew B.
AU - Hanners, Natasha W.
AU - Pöhlmann, Stefan
AU - Gallagher, Tom
AU - Todt, Daniel
AU - Zimmer, Gert
AU - Rice, Charles M.
AU - Schoggins, John W.
AU - Thiel, Volker
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Zoonotic coronaviruses (CoVs) are substantial threats to global health, as exemplified by the emergence of two severe acute respiratory syndrome CoVs (SARS-CoV and SARS-CoV-2) and Middle East respiratory syndrome CoV (MERS-CoV) within two decades1–3. Host immune responses to CoVs are complex and regulated in part through antiviral interferons. However, interferon-stimulated gene products that inhibit CoVs are not well characterized4. Here, we show that lymphocyte antigen 6 complex, locus E (LY6E) potently restricts infection by multiple CoVs, including SARS-CoV, SARS-CoV-2 and 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 immune cells were highly susceptible to a murine CoV—mouse hepatitis virus. Exacerbated viral pathogenesis in Ly6e knockout mice was accompanied by loss of hepatic immune cells, higher splenic viral burden and reduction in global antiviral gene pathways. Accordingly, we found that constitutive Ly6e directly protects primary B cells from murine CoV infection. Our results show 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 CoVs.
AB - Zoonotic coronaviruses (CoVs) are substantial threats to global health, as exemplified by the emergence of two severe acute respiratory syndrome CoVs (SARS-CoV and SARS-CoV-2) and Middle East respiratory syndrome CoV (MERS-CoV) within two decades1–3. Host immune responses to CoVs are complex and regulated in part through antiviral interferons. However, interferon-stimulated gene products that inhibit CoVs are not well characterized4. Here, we show that lymphocyte antigen 6 complex, locus E (LY6E) potently restricts infection by multiple CoVs, including SARS-CoV, SARS-CoV-2 and 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 immune cells were highly susceptible to a murine CoV—mouse hepatitis virus. Exacerbated viral pathogenesis in Ly6e knockout mice was accompanied by loss of hepatic immune cells, higher splenic viral burden and reduction in global antiviral gene pathways. Accordingly, we found that constitutive Ly6e directly protects primary B cells from murine CoV infection. Our results show 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 CoVs.
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U2 - 10.1038/s41564-020-0769-y
DO - 10.1038/s41564-020-0769-y
M3 - Article
C2 - 32704094
AN - SCOPUS:85088456281
SN - 2058-5276
VL - 5
SP - 1330
EP - 1339
JO - Nature microbiology
JF - Nature microbiology
IS - 11
ER -