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Full title:A Coxsackievirus B1-infected neonatal rhesus macaques HFMD model and viral tissue tropism
  • +15
  • * zhanlong,
  • Duan suqin,
  • Li yongjie,
  • Zhang wei,
  • Ming Zhang,
  • * Li yanyan,
  • Zhao yuan,
  • Jin weihua,
  • Liu quan,
  • Li mingxue,
  • Sun wenting,
  • Chen lixiong,
  • Xu hongjie,
  • Tang jie,
  • Hou jinghan,
  • Deng zijun,
  • Yang fengmei,
  • Shaohui Ma
* zhanlong
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medical Biology

Corresponding Author:hzl@imbcams.com.cn

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Duan suqin
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medical Biology
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Li yongjie
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medical Biology
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Zhang wei
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medical Biology
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Ming Zhang
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medical Biology
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* Li yanyan
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medical Biology
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Zhao yuan
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medical Biology
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Jin weihua
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medical Biology
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Liu quan
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medical Biology
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Li mingxue
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medical Biology
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Sun wenting
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medical Biology
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Chen lixiong
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medical Biology
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Xu hongjie
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medical Biology
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Tang jie
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medical Biology
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Hou jinghan
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medical Biology
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Deng zijun
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medical Biology
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Yang fengmei
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medical Biology
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Shaohui Ma
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medical Biology
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Abstract

Coxsackie virus B1 (CVB1) is an enterovirus that presents as hand, foot and mouth disease (HFMD), which may cause long-term symptoms in some patients. However, CVB1 animal models, detoxification cycles, and long-term tissue tropism have not been systematically characterized. In this study, a CVB1 respiratory infection model was established in rhesus macaques, and clinical symptoms, viral load, and immune marker levels were observed in the acute phase (0-14 days) and long-term recovery phase (15-30 days). We also quantified the distribution, replication, and pathology of CVB1 during the long-term recovery period using 35 postmortem rhesus macaques tissue samples at 30 days post infection (d.p.i), thus revealing the long-term tissue tropism of the virus. The results showed that the respiratory tract of rhesus macaques was susceptible to CVB1 and showed HFMD symptoms, detoxification phenomena, changes in cytokine levels, and neutralizing antibodies. Autopsy viral load results were positive in heart, spleen, pancreas, pharyngeal flat, and olfactory bulb tissues, and HE staining revealed pathological damage to the liver, spleen, lung, pharyngeal flat, palatal flat, and tracheal epithelium. Viral antigens were present in visceral, immune, respiratory, and muscle tissues but not detected in intestinal and neural tissues. Brain tissue was dissected and showed viral meningitis-like changes, and CVB1 antigen expression was observed in occipital, pontine, cerebellar, and spinal cord tissues. This study first provides a basis for elucidating CVB1 pathogenesis in a nonhuman primate HFMD model and then confirms the CVB1 tissue tropism pattern after long-term infection.
26 May 2023Submitted to Journal of Medical Virology
30 May 2023Submission Checks Completed
30 May 2023Assigned to Editor
30 May 2023Review(s) Completed, Editorial Evaluation Pending
07 Jun 2023Reviewer(s) Assigned
04 Jul 2023Editorial Decision: Revise Major
28 Jul 20231st Revision Received
21 Aug 2023Submission Checks Completed
21 Aug 2023Assigned to Editor
21 Aug 2023Review(s) Completed, Editorial Evaluation Pending
21 Aug 2023Reviewer(s) Assigned
08 Sep 2023Editorial Decision: Revise Major
29 Jan 2024Review(s) Completed, Editorial Evaluation Pending
30 Jan 2024Editorial Decision: Revise Minor
06 Feb 20243rd Revision Received
06 Feb 2024Submission Checks Completed
06 Feb 2024Assigned to Editor
23 Feb 2024Editorial Decision: Revise Minor
09 Apr 2024Review(s) Completed, Editorial Evaluation Pending
09 Apr 2024Reviewer(s) Assigned
11 Apr 2024Editorial Decision: Accept