{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T18:37:13Z","timestamp":1768502233029,"version":"3.49.0"},"posted":{"date-parts":[[2023,1,26]]},"group-title":"Microbiology","reference-count":56,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,1,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  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\n                  <jats:italic>Ly6e<\/jats:italic>\n                  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\n                  <jats:italic>Ly6e<\/jats:italic>\n                  in\n                  <jats:italic>Lyz2<\/jats:italic>\n                  -expressing cells and radioresistant\n                  <jats:italic>Vav1<\/jats:italic>\n                  -expressing cells were more susceptible to lethal murine coronavirus infection. Mice lacking\n                  <jats:italic>Ly6e<\/jats:italic>\n                  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\n                  <jats:italic>Ly6e<\/jats:italic>\n                  knockout mice revealed a striking reduction of secretory cell-associated genes in infected knockout mice, including\n                  <jats:italic>Muc5b<\/jats:italic>\n                  , 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.\n                <\/jats:p>","DOI":"10.1101\/2023.01.25.525551","type":"posted-content","created":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T16:36:35Z","timestamp":1674750995000},"source":"Crossref","is-referenced-by-count":1,"title":["LY6E protects mice from pathogenic effects of murine coronavirus and SARS-CoV-2"],"prefix":"10.64898","author":[{"given":"Katrina B.","family":"Mar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marley C.","family":"Van Dyke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra H.","family":"Lopez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer L.","family":"Eitson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenchun","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natasha W.","family":"Hanners","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bret M.","family":"Evers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John M.","family":"Shelton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7944-6800","authenticated-orcid":false,"given":"John W.","family":"Schoggins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023012716301063000_2023.01.25.525551v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2014.05.009"},{"key":"2023012716301063000_2023.01.25.525551v1.2","doi-asserted-by":"crossref","unstructured":"Bacquin, A. , C. Bireau , M. Tanguy , C. Romanet , C. Vernochet , A. Dupressoir , and T. Heidmann . 2017. \u2018A Cell Fusion-Based Screening Method Identifies Glycosylphosphatidylinositol-Anchored Protein Ly6e as the Receptor for Mouse Endogenous Retroviral Envelope Syncytin-A\u2019, J Virol, 91.","DOI":"10.1128\/JVI.00832-17"},{"key":"2023012716301063000_2023.01.25.525551v1.3","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1038\/s41586-020-2312-y","article-title":"The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice","volume":"583","year":"2020","journal-title":"Nature"},{"key":"2023012716301063000_2023.01.25.525551v1.4","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2199-11-22"},{"key":"2023012716301063000_2023.01.25.525551v1.5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.12.5296"},{"key":"2023012716301063000_2023.01.25.525551v1.6","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.5.3097-3106.2005"},{"key":"2023012716301063000_2023.01.25.525551v1.7","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.immuni.2015.12.022","article-title":"Central Nervous System Stromal Cells Control Local CD8(+) T Cell Responses during Virus-Induced Neuroinflammation","volume":"44","year":"2016","journal-title":"Immunity"},{"key":"2023012716301063000_2023.01.25.525551v1.8","doi-asserted-by":"crossref","first-page":"e1010464","DOI":"10.1371\/journal.ppat.1010464","article-title":"Inducible CRISPR activation screen for interferon-stimulated genes identifies OAS1 as a SARS-CoV-2 restriction factor","volume":"18","year":"2022","journal-title":"PLoS Pathog"},{"key":"2023012716301063000_2023.01.25.525551v1.9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0188251"},{"key":"2023012716301063000_2023.01.25.525551v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2708-8"},{"key":"2023012716301063000_2023.01.25.525551v1.11","doi-asserted-by":"crossref","first-page":"103277","DOI":"10.1016\/j.ebiom.2021.103277","article-title":"Shared genetic etiology between idiopathic pulmonary fibrosis and COVID-19 severity","volume":"65","author":"Covid-Host Genetics Initiative","year":"2021","journal-title":"EBioMedicine"},{"key":"2023012716301063000_2023.01.25.525551v1.12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009292"},{"key":"2023012716301063000_2023.01.25.525551v1.13","doi-asserted-by":"publisher","DOI":"10.1126\/SCIIMMUNOL.ABL9929"},{"key":"2023012716301063000_2023.01.25.525551v1.14","first-page":"175766","article-title":"Mild or Moderate Covid-19","volume":"383","year":"2020","journal-title":"N Engl J Med"},{"key":"2023012716301063000_2023.01.25.525551v1.15","doi-asserted-by":"publisher","DOI":"10.3109\/13550289709031188"},{"key":"2023012716301063000_2023.01.25.525551v1.16","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc4730"},{"key":"2023012716301063000_2023.01.25.525551v1.17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1720032115"},{"key":"2023012716301063000_2023.01.25.525551v1.18","doi-asserted-by":"crossref","first-page":"103381","DOI":"10.1016\/j.ebiom.2021.103381","article-title":"Q493K and Q498H substitutions in Spike promote adaptation of SARS-CoV-2 in mice","volume":"67","year":"2021","journal-title":"EBioMedicine"},{"key":"2023012716301063000_2023.01.25.525551v1.19","doi-asserted-by":"crossref","unstructured":"Imai, M. , P. J. Halfmann , S. Yamayoshi , K. Iwatsuki-Horimoto , S. Chiba , T. Watanabe , N. Nakajima , M. Ito , M. Kuroda , M. Kiso , T. Maemura , K. Takahashi , S. Loeber , M. Hatta , M. Koga , H. Nagai , S. Yamamoto , M. Saito , E. Adachi , O. Akasaka , M. Nakamura , I. Nakachi , T. Ogura , R. Baba , K. Fujita , J. Ochi , K. Mitamura , H. Kato , H. Nakajima , K. Yagi , S. I. Hattori , K. Maeda , T. Suzuki , Y. Miyazato , R. Valdez , C. Gherasim , Y. Furusawa , M. Okuda , M. Ujie , T. J. S. Lopes , A. Yasuhara , H. Ueki , Y. Sakai-Tagawa , A. J. Eisfeld , J. J. Baczenas , D. A. Baker , S. L. O\u2019Connor , D. H. O\u2019Connor , S. Fukushi , T. Fujimoto , Y. Kuroda , A. Gordon , K. Maeda , N. Ohmagari , N. Sugaya , H. Yotsuyanagi , H. Mitsuya , T. Suzuki , and Y. Kawaoka . 2021. \u2018Characterization of a new SARS-CoV-2 variant that emerged in Brazil\u2019, Proc Natl Acad Sci U S A, 118.","DOI":"10.1073\/pnas.2106535118"},{"key":"2023012716301063000_2023.01.25.525551v1.20","doi-asserted-by":"crossref","unstructured":"Jhingran, A. , S. Kasahara , and T. M. Hohl . 2016. \u2018Flow Cytometry of Lung and Bronchoalveolar Lavage Fluid Cells from Mice Challenged with Fluorescent Aspergillus Reporter (FLARE) Conidia\u2019, Bio Protoc, 6.","DOI":"10.21769\/BioProtoc.1927"},{"key":"2023012716301063000_2023.01.25.525551v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2013.10.010"},{"key":"2023012716301063000_2023.01.25.525551v1.22","doi-asserted-by":"publisher","DOI":"10.1038\/nature07207"},{"key":"2023012716301063000_2023.01.25.525551v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-22040-2"},{"key":"2023012716301063000_2023.01.25.525551v1.24","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0113014"},{"key":"2023012716301063000_2023.01.25.525551v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.09.050"},{"key":"2023012716301063000_2023.01.25.525551v1.26","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1038\/s41467-022-30134-9","article-title":"Identification of DAXX as a restriction factor of SARS-CoV-2 through a CRISPR\/Cas9 screen","volume":"13","year":"2022","journal-title":"Nat Commun"},{"key":"2023012716301063000_2023.01.25.525551v1.27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.12.5910"},{"key":"2023012716301063000_2023.01.25.525551v1.28","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.dci.2009.11.008","article-title":"Cloning and functional characterization of chicken stem cell antigen 2","volume":"34","year":"2010","journal-title":"Dev Comp Immunol"},{"key":"2023012716301063000_2023.01.25.525551v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06000-y"},{"key":"2023012716301063000_2023.01.25.525551v1.30","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.3389\/fimmu.2017.01618","article-title":"Promoter Specificity and Efficacy in Conditional and Inducible Transgenic Targeting of Lung Macrophages","volume":"8","year":"2017","journal-title":"Front Immunol"},{"key":"2023012716301063000_2023.01.25.525551v1.31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001284"},{"key":"2023012716301063000_2023.01.25.525551v1.32","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.5.2355"},{"key":"2023012716301063000_2023.01.25.525551v1.33","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201546108"},{"key":"2023012716301063000_2023.01.25.525551v1.34","doi-asserted-by":"crossref","first-page":"L712","DOI":"10.1152\/ajplung.00305.2021","article-title":"Angiotensin-converting enzyme 2 in peripheral lung club cells modulates the susceptibility to SARS-CoV-2 in chronic obstructive pulmonary disease","volume":"322","year":"2022","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2023012716301063000_2023.01.25.525551v1.35","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1038\/s41564-020-0769-y","article-title":"LY6E impairs coronavirus fusion and confers immune control of viral disease","volume":"5","year":"2020","journal-title":"Nat Microbiol"},{"key":"2023012716301063000_2023.01.25.525551v1.36","doi-asserted-by":"crossref","first-page":"e3001143","DOI":"10.1371\/journal.pbio.3001143","article-title":"Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes","volume":"19","year":"2021","journal-title":"PLoS Biol"},{"key":"2023012716301063000_2023.01.25.525551v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/nature12807"},{"key":"2023012716301063000_2023.01.25.525551v1.38","doi-asserted-by":"crossref","first-page":"5574","DOI":"10.4049\/jimmunol.155.12.5574","article-title":"Modulation of TCR-mediated signaling pathway by thymic shared antigen-1 (TSA-1)\/stem cell antigen-2 (Sca-2)","volume":"155","year":"1995","journal-title":"J Immunol"},{"key":"2023012716301063000_2023.01.25.525551v1.39","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/s41586-020-3014-1","article-title":"Progenitor identification and SARS-CoV-2 infection in human distal lung organoids","volume":"588","year":"2020","journal-title":"Nature"},{"key":"2023012716301063000_2023.01.25.525551v1.40","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1146\/annurev-virology-092818-015756","article-title":"Interferon-Stimulated Genes: What Do They All Do?","volume":"6","year":"2019","journal-title":"Annu Rev Virol"},{"key":"2023012716301063000_2023.01.25.525551v1.41","doi-asserted-by":"publisher","DOI":"10.1038\/nature12862"},{"key":"2023012716301063000_2023.01.25.525551v1.42","doi-asserted-by":"publisher","DOI":"10.1038\/nature09907"},{"key":"2023012716301063000_2023.01.25.525551v1.43","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.120.052318"},{"key":"2023012716301063000_2023.01.25.525551v1.44","doi-asserted-by":"crossref","first-page":"e0124121","DOI":"10.1128\/JVI.01241-21","article-title":"Distinct Roles of Type I and Type III Interferons during a Native Murine beta Coronavirus Lung Infection","volume":"96","year":"2022","journal-title":"J Virol"},{"key":"2023012716301063000_2023.01.25.525551v1.45","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0124661"},{"key":"2023012716301063000_2023.01.25.525551v1.46","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25903-x"},{"key":"2023012716301063000_2023.01.25.525551v1.47","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0590-4"},{"key":"2023012716301063000_2023.01.25.525551v1.48","first-page":"668024","article-title":"The MUC5B Promoter Polymorphism Associates With Severe COVID-19 in the European Population","volume":"8","year":"2021","journal-title":"Front Med (Lausanne)"},{"key":"2023012716301063000_2023.01.25.525551v1.49","doi-asserted-by":"crossref","unstructured":"Verma, Anurag , Jessica Minnier , Jennifer E Huffman , Emily S Wan , Lina Gao , Jacob Joseph , Yuk-Lam Ho , Wen-Chih Wu , Kelly Cho , Bryan R Gorman , Nallakkandi Rajeevan , Saiju Pyarajan , Helene Garcon , James B Meigs , Yan V Sun , Peter D Reaven , John E McGeary , Ayako Suzuki , Joel Gelernter , Julie A Lynch , Jeffrey M Petersen , Seyedeh Maryam Zekavat , Pradeep Natarajan , Cecelia J Madison , Sharvari Dalal , Darshana N Jhala , Mehrdad Arjomandi , Elise Gatsby , Kristine E Lynch , Robert A Bonomo , Mat Freiberg , Gita A Pathak , Jin J Zhou , Curtis J Donskey , Ravi K Madduri , Quinn S Wells , Rose DL Huang , Renato Polimanti , Kyong-Mi Chang , Katherine P Liao , Philip S Tsao , Peter W. F. Wilson , Adriana Hung , Christopher J O\u2019Donnell , John M Gaziano , Richard L Hauger , Sudha K. Iyengar , and Shiuh-Wen Luoh . 2021. \u2018A MUC5B gene polymorphism, rs35705950-T, confers protective effects in COVID-19 infection\u2019, medRxiv: 2021.09.28.21263911.","DOI":"10.1101\/2021.09.28.21263911"},{"key":"2023012716301063000_2023.01.25.525551v1.50","doi-asserted-by":"crossref","first-page":"eabj3624","DOI":"10.1126\/science.abj3624","article-title":"A prenylated dsRNA sensor protects against severe COVID-19","volume":"374","author":"Isaric C.Investigators","year":"2021","journal-title":"Science"},{"key":"2023012716301063000_2023.01.25.525551v1.51","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1038\/s41590-020-0778-2","article-title":"SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function","volume":"21","year":"2020","journal-title":"Nat Immunol"},{"key":"2023012716301063000_2023.01.25.525551v1.52","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830250217"},{"key":"2023012716301063000_2023.01.25.525551v1.53","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401249"},{"key":"2023012716301063000_2023.01.25.525551v1.54","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.755819"},{"key":"2023012716301063000_2023.01.25.525551v1.55","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.3.946-952.2002"},{"key":"2023012716301063000_2023.01.25.525551v1.56","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/s41586-020-2943-z","article-title":"COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice","volume":"589","year":"2021","journal-title":"Nature"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.01.25.525551","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:11:23Z","timestamp":1768450283000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.01.25.525551"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,26]]},"references-count":56,"URL":"https:\/\/doi.org\/10.1101\/2023.01.25.525551","relation":{},"subject":[],"published":{"date-parts":[[2023,1,26]]},"subtype":"preprint"}}