甲型肝炎病毒细胞适应株在Ⅰ型干扰素受体缺失小鼠体内的感染特征OACSTPCD

Objective To investigate the infectivity of hepatitis A virus(HAV)cell-adapted strain in a type Ⅰ interferon receptor-deficient mouse model.Methods The biological charateristics of HM175/18f were identified,including the viral protein expression and viral proliferation by indirect immunofluorescence,Western blot and real-time quantitative RT-PCR in vitro.Then,type Ⅰ interferon receptor-deficient A129 mice were infected with HM175/18f via intravenous injection.The viral RNA load in serum,feces and liver tissues of infected mice were detected to determine the replication of HAV in vivo.The level of serum alanine aminotransferase(ALT)and HE staining of liver tissues were used to evaluate liver injury.Additionally,the dynamic changes of HAV-specific IgG antibody was detected to assess the humoral immune response induced by HM175/18f.Results A129 mice infected with HM175/18f did not show obvious clinical symptoms,nor was the ALT level significantly elevated.However,viral RNA persisted in the liver tissue of infected mice until 42 days after infection.There was focal infiltration of lymphocytes and neutrophils in the liver tissue of infected mice,but no focal necrosis was observed.More importantly,HM175/18f infection caused significant viremia and sustained fecal virus shedding.In addition,HM175/18f induced a significant HAV-specific humoral immune response in A129 mice.Conclusion Our study has revealed the infectivity of HAV cell-adapted strain HM175/18f in type Ⅰ interferon receptor-deficient mice,and identified the attenuated characteristics of HM175/18f,which not only contributes to our understanding of the pathogenesis of HAV,but also expand the applications of a type Ⅰ interferon receptor-deficient mouse model in the study of hepatitis A.