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建立新的肝炎病毒感染动物模型:中国土拨鼠对土拨鼠肝炎病毒感染的易感性。

Establishing a new animal model for hepadnaviral infection: susceptibility of Chinese Marmota-species to woodchuck hepatitis virus infection.

机构信息

Division of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.

出版信息

J Gen Virol. 2011 Mar;92(Pt 3):681-91. doi: 10.1099/vir.0.025023-0. Epub 2010 Nov 17.

Abstract

Hepatitis B virus infection (HBV) is a major medical problem in China. The lack of a suitable infection model in China is recognized as an obstacle for research on HBV in China. Chinese Marmota-species is phylogenetically closely related to Marmota monax, thus, it might be suitable to serve as an animal model for HBV infection. Therefore, we attempted to prove the claim about the existence of woodchuck hepatitis virus (WHV)-like viruses in Chinese Marmota-species and to determine the susceptibility of these species to experimental WHV infection. In the present study, 653 sera from three Chinese Marmota-species, Marmota himalayana, Marmota baibacina and Marmota bobak, were screened for WHV-like viruses by serological and molecular assays. The susceptibility to WHV of three species was investigated by experimental infection and monitored by testing of anti-WHc and WHsAg by ELISA, detection of WHV DNA by PCR, and detection of WHV replication intermediates and antigens in liver samples. No evidence for the existence of a genetically closely related virus to WHV in three Chinese Marmota-species was found by serological assays and PCR. M. himalayana was susceptible to WHV infection as inoculated animals became positive for anti-WHc, WHsAg and WHV DNA. Further, WHV replication intermediates and proteins were detected in liver samples. In contrast, M. baibacina remained negative for tested virological parameters. M. bobak species showed a limited susceptibility to WHV. Our data do not support early reports about WHV-like viruses in China. M. himalayana is suitable for the establishment of a model for hepadnaviral infection.

摘要

乙型肝炎病毒感染(HBV)是中国的一个主要医学问题。中国缺乏合适的感染模型,这被认为是HBV 研究的一个障碍。中国的旱獭属物种与 Marmota monax 在系统发育上密切相关,因此,它可能适合作为乙型肝炎病毒感染的动物模型。因此,我们试图证明中国旱獭属物种中存在土拨鼠肝炎病毒(WHV)样病毒的说法,并确定这些物种对实验性 WHV 感染的敏感性。在本研究中,通过血清学和分子检测方法,对来自三种中国旱獭属物种(Marmota himalayana、Marmota baibacina 和 Marmota bobak)的 653 份血清进行了 WHV 样病毒的筛查。通过实验感染研究了三种物种对 WHV 的易感性,并通过 ELISA 检测抗-WHc 和 WHsAg、PCR 检测 WHV DNA、检测肝组织中 WHV 复制中间体和抗原,监测感染情况。血清学检测和 PCR 未发现三种中国旱獭属物种存在与 WHV 遗传关系密切的病毒。接种动物抗-WHc、WHsAg 和 WHV DNA 均呈阳性,表明 M. himalayana 对 WHV 感染敏感。此外,在肝组织中还检测到了 WHV 复制中间体和蛋白。相比之下,M. baibacina 的所有检测病毒学参数均为阴性。M. bobak 对 WHV 的敏感性有限。我们的数据不支持早期关于中国存在 WHV 样病毒的报道。M. himalayana 适合建立肝病毒感染模型。

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