军事医学2024，Vol.48Issue(9)：650-655,6.DOI:10.7644/j.issn.1674-9960.2024.09.002
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
Infectivity of hepatitis A virus cell-adapted strain in type Ⅰ interferon receptor-deficient mice
高敏 1马青青 1李剑 2阮若彤 1秦成峰 3赵慧1
作者信息
- 1. 军事科学院军事医学研究院,病原微生物生物安全全国重点实验室,北京 100071
- 2. 军事科学院军事医学研究院,病原微生物生物安全全国重点实验室,北京 100071||清华大学药学院,北京 100084
- 3. 军事科学院军事医学研究院,病原微生物生物安全全国重点实验室,北京 100071||中国医学科学院北京协和医学院,自然疫源性疾病发现与溯源创新单元,北京 100730
- 折叠
摘要
Abstract
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.关键词
甲型肝炎/甲型肝炎病毒/细胞适应株/Ⅰ型干扰素受体缺失小鼠/小鼠模型Key words
hepatitis A/hepatitis A virus/cell-adapted strain/type Ⅰ interferon receptor-deficiency mice/mouse model分类
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高敏,马青青,李剑,阮若彤,秦成峰,赵慧..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[J].军事医学,2024,48(9):650-655,6.
