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Article: Mouse models susceptible to HCoV-229E and HCoV-NL63 and cross protection from challenge with SARS-CoV-2

TitleMouse models susceptible to HCoV-229E and HCoV-NL63 and cross protection from challenge with SARS-CoV-2
Authors
Issue Date1-Jan-2023
PublisherNational Academy of Sciences
Citation
Proceedings of the National Academy of Sciences, 2023, v. 120, n. 4 How to Cite?
Abstract

Human coronavirus 229E (HCoV-229E) and NL63 (HCoV-NL63) are endemic causes of upper respiratory infections such as the "common cold" 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-/- and STAT1-/- 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.


Persistent Identifierhttp://hdl.handle.net/10722/328352
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 3.737

 

DC FieldValueLanguage
dc.contributor.authorLiu, Donglan-
dc.contributor.authorChen, Chunke-
dc.contributor.authorChen, Dingbin-
dc.contributor.authorZhu, Airu-
dc.contributor.authorLi, Fang-
dc.contributor.authorZhuang, Zhen-
dc.contributor.authorMok, Chris Ka Pun-
dc.contributor.authorDai, Jun-
dc.contributor.authorLi, Xiaobo-
dc.contributor.authorJin, Yingkang-
dc.contributor.authorChen, Zhao-
dc.contributor.authorSun, Jing-
dc.contributor.authorWang, Yanqun-
dc.contributor.authorLi, Yuming-
dc.contributor.authorZhang, Yanjun-
dc.contributor.authorWen, Liyan-
dc.contributor.authorZhang, Zhaoyong-
dc.contributor.authorZhuo, Jianfen-
dc.contributor.authorWang, Junxiang-
dc.contributor.authorRan, Wei-
dc.contributor.authorWang, Dong-
dc.contributor.authorZhang, Shengnan-
dc.contributor.authorTang, Yanhong-
dc.contributor.authorLi, Suxiang-
dc.contributor.authorLai, Xiaoming-
dc.contributor.authorWei, Peilan-
dc.contributor.authorYuan, Jinwei-
dc.contributor.authorChen, Fangli-
dc.contributor.authorHuang, Shuxiang-
dc.contributor.authorSun, Fangfang-
dc.contributor.authorQian, Zhaohui-
dc.contributor.authorTan, Wenjie-
dc.contributor.authorZhao, Jingxian-
dc.contributor.authorPeiris, Malik-
dc.contributor.authorZhao, Jincun-
dc.date.accessioned2023-06-28T04:42:59Z-
dc.date.available2023-06-28T04:42:59Z-
dc.date.issued2023-01-01-
dc.identifier.citationProceedings of the National Academy of Sciences, 2023, v. 120, n. 4-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/328352-
dc.description.abstract<p>Human coronavirus 229E (HCoV-229E) and NL63 (HCoV-NL63) are endemic causes of upper respiratory infections such as the "common cold" 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<sup>-/-</sup> and STAT1<sup>-/-</sup> 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.<br></p>-
dc.languageeng-
dc.publisherNational Academy of Sciences-
dc.relation.ispartofProceedings of the National Academy of Sciences-
dc.titleMouse models susceptible to HCoV-229E and HCoV-NL63 and cross protection from challenge with SARS-CoV-2-
dc.typeArticle-
dc.identifier.doi10.1073/pnas.2202820120-
dc.identifier.hkuros344690-
dc.identifier.volume120-
dc.identifier.issue4-
dc.identifier.eissn1091-6490-
dc.identifier.issnl0027-8424-

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