Guilhot S, Huang S N, Xia Y P, La Monica N, Lai M M, Chisari F V
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037.
J Virol. 1994 Feb;68(2):1052-8. doi: 10.1128/JVI.68.2.1052-1058.1994.
Simultaneous infection with hepatitis delta virus (HDV) and hepatitis B virus (HBV) in humans is often associated with severe viral liver disease including fulminant hepatitis. Since HBV is thought to be noncytopathic to the hepatocyte, the enhanced disease severity observed during dual infection has been attributed to either simultaneous immune responses against the two viruses or direct cytotoxic effects of HDV products on the hepatocyte or both. To examine these alternate possibilities, we produced transgenic mice that express the small and large delta antigens (HDAg) in hepatocyte nuclei at levels equal to those observed during natural HDV infection. No biological or histopathological evidence of liver disease was detectable during 18 months of observation, suggesting that neither the large nor small form of HDAg is directly cytopathic to the hepatocyte in vivo.
人类同时感染丁型肝炎病毒（HDV）和乙型肝炎病毒（HBV）通常与严重的病毒性肝病相关，包括暴发性肝炎。由于HBV被认为对肝细胞无细胞病变作用，因此在双重感染期间观察到的疾病严重程度增加被归因于对两种病毒的同时免疫反应或HDV产物对肝细胞的直接细胞毒性作用，或两者兼而有之。为了研究这些替代可能性，我们培育了转基因小鼠，这些小鼠在肝细胞核中表达小和大丁型肝炎抗原（HDAg），其水平与自然HDV感染期间观察到的水平相当。在18个月的观察期内未检测到肝病的生物学或组织病理学证据，这表明HDAg的大或小形式在体内对肝细胞均无直接细胞病变作用。
