Enhanced intracellular retention of a hepatitis B virus strain associated with fulminant hepatitis
Enhanced intracellular retention of a hepatitis B virus strain associated with fulminant hepatitis
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DOI：
10.1016/j.virol.2009.09.028
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发表时间：
2009-12-20
期刊：
影响因子：
3.7
通讯作者：
Shimosegawa, Tooru
中科院分区：
文献类型：
--
作者：
Inoue, Jun;Ueno, Yoshiyuki;Shimosegawa, Tooru
从连续引起5例暴发性肝炎的HBV毒株（pBFH 2）中构建了携带1.3倍HBV基因组的质粒，并将pBFH 2或其变体转染HepG 2细胞。与野生型构建体相比，具有A1762 T/G1764 A、G1862 T和G1896 A的pBFH 2构建体显示出最大量的核心颗粒相关的细胞内HBV DNA，但细胞外HBV DNA没有显著增加，这表明这些突变可能共同作用以将复制中间体保留在细胞中。共聚焦荧光显微镜观察发现，HepG 2细胞内的B型肝炎核心抗原（HBcAg）定位于细胞核内，这可能与HBcAg的滞留有关。连续重型肝炎患者肝组织标本HBcAg免疫组化染色显示细胞核染色强于急性肝炎患者。总之，暴发性HBV毒株引起核心颗粒和核心颗粒相关HBV DNA在细胞中的保留。(C)2009 Elsevier Inc. All rights reserved.
A plasmid carrying 1.3-fold HBV genome was constructed from a HBV strain that caused five consecutive cases of fulminant hepatitis (pBFH2), and HepG2 cells were transfected with pBFH2 or its variants. The pBFH2 construct with A1762T/G1764A, G1862T, and G1896A showed the largest amount of core particle-associated intracellular HBV DNA, but no significant increase of extracellular HBV DNA in comparison with the wild construct, suggesting that these mutations might work together for retention of the replicative intermediates in the cells. The retention might relate to the localization of hepatitis B core antigen (HBcAg) in the nucleus of HepG2, which was observed by confocal fluorescence microscopy. HBcAg immunohistochemical examination of liver tissue samples obtained from the consecutive fulminant hepatitis patients showed stronger staining in the nucleus than acute hepatitis patients. In conclusion, the fulminant HBV strain caused retention of the core particles and the core particle-associated HBV DNA in the cells. (C) 2009 Elsevier Inc. All rights reserved.