LY6E, also known as lymphocyte antigen 6 complex, locus E, is a protein that belongs to the lymphocyte antigen-6/urokinase-type plasminogen activator receptor Ly6/uPAR family. It plays important roles in immunological regulation, T cell physiology, and oncogenesis. Emerging evidence indicates its involvement in modulating viral infection, especially in restricting the entry of coronaviruses and other viruses [2].

Using conditional Ly6e knockout mice, studies have shown that loss of Ly6e in Lyz2-expressing cells, radioresistant Vav1-expressing cells and non-haematopoietic cells increased susceptibility to murine coronavirus. Global conditional loss of Ly6e expression led to clinical disease and higher viral burden after SARS-CoV-2 infection. Ly6e expression protected secretory club and ciliated cells from SARS-CoV-2 infection and maintained an epithelial cell transcriptomic signature in the lung [1,3]. Mice lacking Ly6e in Lyz2-expressing cells and radioresistant Vav1-expressing cells were more susceptible to lethal murine coronavirus infection [3].

In conclusion, Ly6e is a critical antiviral immune effector that restricts coronavirus infection by interfering with spike-protein mediated membrane fusion. The use of Ly6e knockout mouse models has significantly enhanced our understanding of its role in protecting against diseases caused by murine and human coronaviruses, highlighting its potential as a target for antiviral strategies [1,3,4].

References:

1. Mar, Katrina B, Wells, Alexandra I, Caballero Van Dyke, Marley C, Shelton, John M, Schoggins, John W. 2023. LY6E is a pan-coronavirus restriction factor in the respiratory tract. In Nature microbiology, 8, 1587-1599. doi:10.1038/s41564-023-01431-w. https://pubmed.ncbi.nlm.nih.gov/37443277/

2. Yu, Jingyou, Liu, Shan-Lu. 2019. Emerging Role of LY6E in Virus-Host Interactions. In Viruses, 11, . doi:10.3390/v11111020. https://pubmed.ncbi.nlm.nih.gov/31684192/

3. Mar, Katrina B, Van Dyke, Marley C, Lopez, Alexandra H, Shelton, John M, Schoggins, John W. 2023. LY6E protects mice from pathogenic effects of murine coronavirus and SARS-CoV-2. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.01.25.525551. https://pubmed.ncbi.nlm.nih.gov/36747632/

4. Pfaender, Stephanie, Mar, Katrina B, Michailidis, Eleftherios, Schoggins, John W, Thiel, Volker. 2020. LY6E impairs coronavirus fusion and confers immune control of viral disease. In Nature microbiology, 5, 1330-1339. doi:10.1038/s41564-020-0769-y. https://pubmed.ncbi.nlm.nih.gov/32704094/