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

Pfaender, Stephanie; Mar, Katrina B; Michailidis, Eleftherios; Kratzel, Annika; Boys, Ian N; V'kovski, Philip; Fan, Wenchun; Kelly, Jenna N.; Hirt, Dagny; Ebert, Nadine; Stalder, Hanspeter; Kleine-Weber, Hannah; Hoffmann, Markus; Heinrich Hoffmann, H; Saeed, Mohsan; Dijkman, Ronald; Steinmann, Eike; Wight-Carter, Mary; McDougal, Matthew B; Hanners, Natasha W; ... (2020). LY6E impairs coronavirus fusion and confers immune control of viral disease. (In Press). Nature microbiology Springer Nature 10.1038/s41564-020-0769-y

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

UniBE Contributor:

Pfänder, Stephanie; Kratzel, Annika; V'kovski, Philip; Kelly, Jenna Nicole; Hirt, Dagny Nora; Ebert, Nadine; Stalder, Hanspeter; Dijkman, Ronald; Zimmer, Gert and Thiel, Volker Earl

Subjects:

600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2058-5276

Publisher:

Springer Nature

Language:

English

Submitter:

Andrea Stettler

Date Deposited:

03 Aug 2020 12:30

Last Modified:

03 Aug 2020 12:30

Publisher DOI:

10.1038/s41564-020-0769-y

PubMed ID:

32704094

BORIS DOI:

10.7892/boris.145531

URI:

https://boris.unibe.ch/id/eprint/145531

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