Nat Microbiol . LY6E impairs coronavirus fusion and confers immune control of viral disease

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Nat Microbiol


. 2020 Jul 23.
doi: 10.1038/s41564-020-0769-y. Online ahead of print.
LY6E impairs coronavirus fusion and confers immune control of viral disease


Stephanie Pfaender ^{1 2 3} , Katrina B Mar ⁴ , Eleftherios Michailidis ⁵ , Annika Kratzel ^{1 2 6} , Ian N Boys ⁴ , Philip V'kovski ^{1 2} , Wenchun Fan ⁴ , Jenna N Kelly ^{1 2} , Dagny Hirt ^{1 2} , Nadine Ebert ^{1 2} , Hanspeter Stalder ^{1 2} , Hannah Kleine-Weber ^{7 8} , Markus Hoffmann ⁷ , H Heinrich Hoffmann ⁵ , Mohsan Saeed ^{5 9 10} , Ronald Dijkman ^{1 2 11 12} , Eike Steinmann ³ , Mary Wight-Carter ¹³ , Matthew B McDougal ⁴ , Natasha W Hanners ¹⁴ , Stefan P?hlmann ^{7 8} , Tom Gallagher ¹⁵ , Daniel Todt ^{3 12} , Gert Zimmer ^{1 2} , Charles M Rice ¹⁶ , John W Schoggins ¹⁷ , Volker Thiel ^{18 19}



Affiliations

• PMID: 32704094
• DOI: 10.1038/s41564-020-0769-y

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 decades^1-3. 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.