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Citation: Qing-Qing Ma, Hong-Jiang Wang, Jian Li, Meng-Qi Li, Tian-Shu Cao, Xiao-Yan Wu, Hong-Ying Qiu, Hui Zhao, Cheng-Feng Qin. The infectivity and pathogenicity of hepatitis A virus live-attenuated vaccine strain H2 in type I interferon receptor-deficient mice [J].VIROLOGICA SINICA, 2022, 37(5) : 740-745.  http://dx.doi.org/10.1016/j.virs.2022.07.009

The infectivity and pathogenicity of hepatitis A virus live-attenuated vaccine strain H2 in type I interferon receptor-deficient mice

  • Corresponding author: Hui Zhao, shuishu2002@126.com
    Cheng-Feng Qin, qincf@bmi.ac.cn
  • Received Date: 22 April 2022
    Accepted Date: 23 May 2022
    Available online: 19 July 2022
  • Hepatitis A virus (HAV) live-attenuated vaccine H2 strain has been approved for clinical use for decades with ideal safety profiles in nonhuman primate models and humans. Recently, type I interferon (IFN) receptor-deficient mice were shown to be susceptible to HAV infection. Herein, we sought to determine the infection and replication dynamics of the H2 in Ifnar-/- mice that lack type I IFN receptor. Following intravenous injection, the H2 failed to cause obvious clinical symptoms in Ifnar-/- mice, and no significant upregulation in serum alanine aminotransferase (ALT) levels was observed. Notably, the histopathological examination showed that there were significant focal infiltrations of lymphocytes and neutrophils in the portal area, but no focal necrosis was observed in liver tissues. Viral RNAs sustained in the liver, and the infectious virus could be recovered from the liver tissue until 42 days post-infection. More importantly, H2 infection induced obvious viremia and persistent viral shedding in feces. In addition, robust HAV-specific humoral immune responses were induced in Ifnar-/- mice. Overall, our study revealed the safety profile of H2 in Ifnar-/- mice, which not only helps understand the attenuation mechanism of H2, but also expands the application of the Ifnar-/--/- mouse model for HAV studies.

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    The infectivity and pathogenicity of hepatitis A virus live-attenuated vaccine strain H2 in type I interferon receptor-deficient mice

      Corresponding author: Hui Zhao, shuishu2002@126.com
      Corresponding author: Cheng-Feng Qin, qincf@bmi.ac.cn
    • a State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing, 100071, China;

    Abstract: Hepatitis A virus (HAV) live-attenuated vaccine H2 strain has been approved for clinical use for decades with ideal safety profiles in nonhuman primate models and humans. Recently, type I interferon (IFN) receptor-deficient mice were shown to be susceptible to HAV infection. Herein, we sought to determine the infection and replication dynamics of the H2 in Ifnar-/- mice that lack type I IFN receptor. Following intravenous injection, the H2 failed to cause obvious clinical symptoms in Ifnar-/- mice, and no significant upregulation in serum alanine aminotransferase (ALT) levels was observed. Notably, the histopathological examination showed that there were significant focal infiltrations of lymphocytes and neutrophils in the portal area, but no focal necrosis was observed in liver tissues. Viral RNAs sustained in the liver, and the infectious virus could be recovered from the liver tissue until 42 days post-infection. More importantly, H2 infection induced obvious viremia and persistent viral shedding in feces. In addition, robust HAV-specific humoral immune responses were induced in Ifnar-/- mice. Overall, our study revealed the safety profile of H2 in Ifnar-/- mice, which not only helps understand the attenuation mechanism of H2, but also expands the application of the Ifnar-/--/- mouse model for HAV studies.

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