{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:09:49Z","timestamp":1790298589384,"version":"4.1.0"},"reference-count":55,"publisher":"National Academy of Sciences","issue":"4","license":[{"start":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T00:00:00Z","timestamp":1674000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,1,24]]},"abstract":"<jats:p>\n                    Human coronavirus 229E (HCoV-229E) and NL63 (HCoV-NL63) are endemic causes of upper respiratory infections such as the \u201ccommon cold\u201d but may occasionally cause severe lower respiratory tract disease in the elderly and immunocompromised patients. There are no approved antiviral drugs or vaccines for these common cold coronaviruses (CCCoV). The recent emergence of COVID-19 and the possible cross-reactive antibody and T cell responses between these CCCoV and SARS-CoV-2 emphasize the need to develop experimental animal models for CCCoV. Mice are an ideal experimental animal model for such studies, but are resistant to HCoV-229E and HCoV-NL63 infections. Here, we generated 229E and NL63 mouse models by exogenous delivery of their receptors, human hAPN and hACE2 using replication-deficient adenoviruses (Ad5-hAPN and Ad5-hACE2), respectively. Ad5-hAPN- and Ad5-hACE2-sensitized IFNAR\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    and STAT1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice developed pneumonia characterized by inflammatory cell infiltration with virus clearance occurring 7 d post infection. Ad5-hAPN- and Ad5-hACE2-sensitized mice generated virus-specific T cells and neutralizing antibodies after 229E or NL63 infection, respectively. Remdesivir and a vaccine candidate targeting spike protein of 229E and NL63 accelerated viral clearance of virus in these mice. 229E- and NL63-infected mice were partially protected from SARS-CoV-2 infection, likely mediated by cross-reactive T cell responses. Ad5-hAPN- and Ad5-hACE2-transduced mice are useful for studying pathogenesis and immune responses induced by HCoV-229E and HCoV-NL63 infections and for validation of broadly protective vaccines, antibodies, and therapeutics against human respiratory coronaviruses including SARS-CoV-2.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2202820120","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T13:49:27Z","timestamp":1674049767000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":39,"title":["Mouse models susceptible to HCoV-229E and HCoV-NL63 and cross protection from challenge with SARS-CoV-2"],"prefix":"10.1073","volume":"120","author":[{"given":"Donglan","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510182, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunke","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510182, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingbin","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510182, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Airu","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510182, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510182, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhuang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510182, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris Ka Pun","family":"Mok","sequence":"additional","affiliation":[{"name":"The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR, PR China"},{"name":"Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Dai","sequence":"additional","affiliation":[{"name":"Guangzhou Customs District Technology Center, Guangzhou 510700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobo","family":"Li","sequence":"additional","affiliation":[{"name":"Guangzhou Customs District Technology Center, Guangzhou 510700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingkang","family":"Jin","sequence":"additional","affiliation":[{"name":"Pediatric Pulmonary Department, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510182, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510182, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqun","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suxiang","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510182, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Lai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510182, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peilan","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510182, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinwei","family":"Yuan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510182, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangli","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510182, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangzhou Customs District Technology Center, Guangzhou 510700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Sun","sequence":"additional","affiliation":[{"name":"Guangzhou Customs District Technology Center, Guangzhou 510700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Qian","sequence":"additional","affiliation":[{"name":"NHC Key laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100176, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5963-1136","authenticated-orcid":false,"given":"Wenjie","family":"Tan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biosafety, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, Chinese center for disease control and prevention, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxian","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510182, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8217-5995","authenticated-orcid":false,"given":"Malik","family":"Peiris","sequence":"additional","affiliation":[{"name":"Hong Kong University \u2013 Pasteur Research Pole, Hong Kong Special Administrative Region, China"},{"name":"School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,1,18]]},"reference":[{"key":"e_1_3_4_1_2","first-page":"825","volume-title":"Fields Virology","author":"Fields B. 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(Lippincott Williams & Wilkins, 2013), vol. 2, pp. 825\u2013858."},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.03.031"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/135965350701200S01.1"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/irv.12563"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/377612"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit393"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/597122"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0118-9"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.3.5568.767"},{"key":"e_1_3_4_10_2","first-page":"6796839","article-title":"A rare case of human coronavirus 229E associated with acute respiratory distress syndrome in a healthy adult","volume":"2018","author":"Vassilara F.","year":"2018","unstructured":"F. Vassilara , A rare case of human coronavirus 229E associated with acute respiratory distress syndrome in a healthy adult. Case Rep. Infect. Dis. 2018, 6796839 (2018).","journal-title":"Case Rep. Infect. 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Zhuang , Correction: Mapping and role of T cell response in SARS-CoV-2-infected mice. J. Exp. Med. 218, e2020218710052021c (2021).","journal-title":"J. Exp. Med."},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.7573\/dic.2020-4-14"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2007764"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dsx.2020.05.018"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1922083117"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI143380"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd3871"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI143120"},{"key":"e_1_3_4_53_2","doi-asserted-by":"crossref","unstructured":"B. A. Woldemeskel C. C. Garliss J. N. Blankson SARS-CoV-2 mRNA vaccines induce broad CD4+ T cell responses that recognize SARS-CoV-2 variants and HCoV-NL63. J. Clin. Invest. 131 e149335 (2021). e149335","DOI":"10.1172\/JCI149335"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3301197"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0030525"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2202820120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T08:53:17Z","timestamp":1695286397000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2202820120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,18]]},"references-count":55,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,1,24]]}},"alternative-id":["10.1073\/pnas.2202820120"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2202820120","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,18]]},"assertion":[{"value":"2022-02-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2202820120"}}