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Published on: November 5, 2021
LY6E protects mice from pathogenic effects of murine coronavirus and SARS-CoV-2
Abstract:
LY6E is an antiviral protein that inhibits coronavirus entry. Its expression in immune cells allows mice to control murine coronavirus infection. However, it is not known which immune cell subsets mediate this control or whether LY6E protects mice from SARS-CoV-2. In this study, we used tissue-specific Cre recombinase expression to ablate Ly6e in distinct immune compartments or in all epiblast-derived cells, and bone marrow chimeras to target Ly6e in a subset of radioresistant cells. Mice lacking Ly6e in Lyz2 -expressing cells and radioresistant Vav1 -expressing cells were more susceptible to lethal murine coronavirus infection. Mice lacking Ly6e globally developed clinical disease when challenged with the Gamma (P.1) variant of SARS-CoV-2. By contrast, wildtype mice and mice lacking type I and type III interferon signaling had no clinical symptoms after SARS-CoV-2 infection. Transcriptomic profiling of lungs from SARS-CoV-2-infected wildtype and Ly6e knockout mice revealed a striking reduction of secretory cell-associated genes in infected knockout mice, including Muc5b , an airway mucin-encoding gene that may protect against SARS-CoV-2-inflicted respiratory disease. Collectively, our study reveals distinct cellular compartments in which Ly6e confers cell intrinsic antiviral effects, thereby conferring resistance to disease caused by murine coronavirus and SARS-CoV-2.
Insights
The antiviral protein LY6E protects mice from coronavirus infections. Its absence in specific immune cells increases susceptibility to murine coronavirus and SARS-CoV-2, highlighting LY6E
Area of Science:
- Virology and Immunology
- Host-pathogen interactions
Background:
- LY6E is an antiviral protein known to inhibit coronavirus entry and control murine coronavirus infection in mice.
- The specific immune cell subsets mediating LY6E's antiviral effects and its role in protection against SARS-CoV-2 remain largely unknown.
Approach:
- Utilized tissue-specific Cre recombinase expression to ablate Ly6e in distinct immune cell compartments and epiblast-derived cells.
- Employed bone marrow chimeras to investigate Ly6e's function in radioresistant cells.
- Challenged mice with murine coronavirus and the Gamma (P.1) variant of SARS-CoV-2, followed by transcriptomic profiling of lung tissues.
Key Points:
- Mice lacking Ly6e in Lyz2-expressing cells or radioresistant Vav1-expressing cells showed increased susceptibility to lethal murine coronavirus infection.
- Global Ly6e knockout mice developed clinical disease upon SARS-CoV-2 challenge, unlike wildtype or interferon-deficient mice.
- SARS-CoV-2 infected Ly6e knockout mice exhibited reduced expression of secretory cell-associated genes, including Muc5b, crucial for airway protection.
Conclusions:
- LY6E confers cell-intrinsic antiviral effects within specific immune cell compartments, providing resistance against murine coronavirus and SARS-CoV-2.
- LY6E plays a critical role in host defense against SARS-CoV-2, potentially through the regulation of protective airway mucins.
