LY6E impairs coronavirus fusion and confers immune control of viral disease

Stephanie Pfaender, Katrina B. Mar, Eleftherios Michailidis, Annika Kratzel, Ian N. Boys, Philip V’kovski, Wenchun Fan, Jenna N. Kelly, Dagny Hirt, Nadine Ebert, Hanspeter Stalder, Hannah Kleine-Weber, Markus Hoffmann, Hans Heinrich Hoffmann, Mohsan Saeed, Ronald Dijkman, Eike Steinmann, Mary Wight-Carter, Matthew B. McDougal, Natasha W. HannersStefan Pöhlmann, Tom Gallagher, Daniel Todt, Gert Zimmer, Charles M. Rice, John W. Schoggins, Volker Thiel

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1330-1339
Number of pages10
JournalNature microbiology
Volume5
Issue number11
DOIs
StatePublished - Nov 1 2020

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Applied Microbiology and Biotechnology
  • Genetics
  • Microbiology (medical)
  • Cell Biology

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