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Detection of H1N1 Influenza Virus in the Bile of a Severe Influenza Mouse Model
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  • Yan Liu,
  • Jiuyang Xu,
  • Cheng Wei,
  • Yitian Xu,
  • Chen Lyu,
  • Mingzhi Sun,
  • Ying Zheng,
  • Bin Cao
Yan Liu
China-Japan Friendship Hospital
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Jiuyang Xu
China-Japan Friendship Hospital
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Cheng Wei
Peking University
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Yitian Xu
Peking Union Medical College Hospital
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Chen Lyu
Peking Union Medical College Hospital
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Mingzhi Sun
Tsinghua University School of Medicine
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Ying Zheng
Capital Medical University
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Bin Cao
China-Japan Friendship Hospital

Corresponding Author:caobin_ben@163.com

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Abstract

Influenza virus infection may lead to fatal complications including multi-organ failure and sepsis. The influenza virus was detected in various extra-pulmonary organs in autopsy studies during the 2009 pandemic. However, limited research has been conducted on the presence of viral particle or viral components in the peripheral blood. We established a mouse model for severe H1N1 influenza. The bile and blood samples were collected over time and inoculated into embryonated chicken eggs. We detected live influenza virus with plaque assay test and negative stain with electronic microscopy in bile and blood samples in early infection. Immunofluorescence showed influenza viral components in the liver tissue. No live virus was isolated in the bile in mice intragastrically administered with influenza virus, indicating that the virus was spread from the blood stream. Targeted metabolomics analysis of bile acid and liver tissues showed that a secondary bile acid (3-dehydrocholic acid) was decreased after influenza H1N1 infection. Genes related with fatty acid metabolism and bile secretion pathways were down-regulated in liver after influenza virus infection. Our study indicated that influenza virus viremia is present in severe influenza, and that the liver is a target organ for influenza viral sepsis.
09 May 2024Submitted to Influenza and other respiratory viruses
10 May 2024Submission Checks Completed
10 May 2024Assigned to Editor
18 Jun 2024Review(s) Completed, Editorial Evaluation Pending
20 Jun 2024Editorial Decision: Revise Major
20 Aug 20241st Revision Received
26 Aug 2024Submission Checks Completed
26 Aug 2024Assigned to Editor
07 Sep 2024Review(s) Completed, Editorial Evaluation Pending
09 Sep 2024Editorial Decision: Accept