tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2023 Jan 24;120(4):e2202820120.
doi: 10.1073/pnas.2202820120. Epub 2023 Jan 18.
Mouse models susceptible to HCoV-229E and HCoV-NL63 and cross protection from challenge with SARS-CoV-2
Donglan Liu[SUP] 1 [/SUP], Chunke Chen[SUP] 1 [/SUP], Dingbin Chen[SUP] 1 [/SUP], Airu Zhu[SUP] 1 [/SUP], Fang Li[SUP] 1 [/SUP], Zhen Zhuang[SUP] 1 [/SUP], Chris Ka Pun Mok[SUP] 2 3 [/SUP], Jun Dai[SUP] 4 [/SUP], Xiaobo Li[SUP] 4 [/SUP], Yingkang Jin[SUP] 5 [/SUP], Zhao Chen[SUP] 1 [/SUP], Jing Sun[SUP] 1 [/SUP], Yanqun Wang[SUP] 1 [/SUP], Yuming Li[SUP] 1 [/SUP], Yanjun Zhang[SUP] 1 [/SUP], Liyan Wen[SUP] 1 [/SUP], Zhaoyong Zhang[SUP] 1 [/SUP], Jianfen Zhuo[SUP] 1 [/SUP], Junxiang Wang[SUP] 1 [/SUP], Wei Ran[SUP] 1 [/SUP], Dong Wang[SUP] 1 [/SUP], Shengnan Zhang[SUP] 1 [/SUP], Yanhong Tang[SUP] 1 [/SUP], Suxiang Li[SUP] 1 [/SUP], Xiaoming Lai[SUP] 1 [/SUP], Peilan Wei[SUP] 1 [/SUP], Jinwei Yuan[SUP] 1 [/SUP], Fangli Chen[SUP] 1 [/SUP], Shuxiang Huang[SUP] 4 [/SUP], Fangfang Sun[SUP] 4 [/SUP], Zhaohui Qian[SUP] 6 [/SUP], Wenjie Tan[SUP] 7 [/SUP], Jingxian Zhao[SUP] 1 [/SUP], Malik Peiris[SUP] 8 9 [/SUP], Jincun Zhao[SUP] 1 10 11 12 13 [/SUP]
Affiliations
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[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.
Keywords: HCoV-229E; HCoV-NL63; SARS-CoV-2; mouse model; therapeutics; vaccine.
. 2023 Jan 24;120(4):e2202820120.
doi: 10.1073/pnas.2202820120. Epub 2023 Jan 18.
Mouse models susceptible to HCoV-229E and HCoV-NL63 and cross protection from challenge with SARS-CoV-2
Donglan Liu[SUP] 1 [/SUP], Chunke Chen[SUP] 1 [/SUP], Dingbin Chen[SUP] 1 [/SUP], Airu Zhu[SUP] 1 [/SUP], Fang Li[SUP] 1 [/SUP], Zhen Zhuang[SUP] 1 [/SUP], Chris Ka Pun Mok[SUP] 2 3 [/SUP], Jun Dai[SUP] 4 [/SUP], Xiaobo Li[SUP] 4 [/SUP], Yingkang Jin[SUP] 5 [/SUP], Zhao Chen[SUP] 1 [/SUP], Jing Sun[SUP] 1 [/SUP], Yanqun Wang[SUP] 1 [/SUP], Yuming Li[SUP] 1 [/SUP], Yanjun Zhang[SUP] 1 [/SUP], Liyan Wen[SUP] 1 [/SUP], Zhaoyong Zhang[SUP] 1 [/SUP], Jianfen Zhuo[SUP] 1 [/SUP], Junxiang Wang[SUP] 1 [/SUP], Wei Ran[SUP] 1 [/SUP], Dong Wang[SUP] 1 [/SUP], Shengnan Zhang[SUP] 1 [/SUP], Yanhong Tang[SUP] 1 [/SUP], Suxiang Li[SUP] 1 [/SUP], Xiaoming Lai[SUP] 1 [/SUP], Peilan Wei[SUP] 1 [/SUP], Jinwei Yuan[SUP] 1 [/SUP], Fangli Chen[SUP] 1 [/SUP], Shuxiang Huang[SUP] 4 [/SUP], Fangfang Sun[SUP] 4 [/SUP], Zhaohui Qian[SUP] 6 [/SUP], Wenjie Tan[SUP] 7 [/SUP], Jingxian Zhao[SUP] 1 [/SUP], Malik Peiris[SUP] 8 9 [/SUP], Jincun Zhao[SUP] 1 10 11 12 13 [/SUP]
Affiliations
- PMID: 36652473
- DOI: 10.1073/pnas.2202820120
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[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.
Keywords: HCoV-229E; HCoV-NL63; SARS-CoV-2; mouse model; therapeutics; vaccine.