Integration of HBV-DNA into liver and hepatocellular carcinoma cells during persistent HBV infection.
Integration of HBV-DNA into liver and hepatocellular carcinoma cells during persistent HBV infection.
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持续 HBV 感染期间 HBV-DNA 整合到肝脏和肝细胞癌细胞中。
DOI：
10.1002/jcb.240200310
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发表时间：
1982
影响因子：
4
通讯作者：
Shafritz,DA
中科院分区：
文献类型：
--
作者：
Shafritz,DA
乙型肝炎病毒携带状态（持续性HBV感染）的特征是血液中存在病毒表面抗原（HBsAg）和病毒颗粒（Dane颗粒）。 1% 至 10% 的携带者会患上慢性肝病和/或肝细胞癌。最近的研究表明，肝细胞癌和几种人肝癌细胞系中存在整合的 HBV-DNA。在肝癌患者中，所有 HBsAg 携带者中都发现了整合的 HBV-DNA。非肿瘤肝脏还显示出整合的 HBV-DNA，其杂交模式与在肿瘤中观察到的杂交模式相同或不同。为了探讨整合何时发生，对短期（<2 年）或长期（> 8-10 年）的携带者进行了评估。经皮（针）肝活检的 DNA 提取物显示游离病毒 DNA，在短期携带者中没有特定的整合带。在长期携带者中，HBV-DNA 以扩散或独特的杂交模式整合到宿主基因组中。 HBV-DNA 整合与携带状态的持续时间和血清中病毒颗粒的缺失相关，但与慢性肝炎的组织学证据无关。这些研究表明，无论肝脏疾病如何，HBV-DNA 的整合都会发生在持续 HBV 感染期间，并且发生在肝细胞癌的发展之前。
The hepatitis B virus carrier state (persistent HBV infection) is characterized by the presence of viral surface antigen (HBsAg) and virion particles (Dane particles) in the blood. From 1% to 10% of carriers develop chronic liver disease and/or hepatocellular carcinoma. Recent studies have demonstrated integrated HBV‐DNA in hepatocellular carcinomas and in several human hepatoma cell lines. In hepatoma patients, integrated HBV‐DNA has been found in all HBsAg carriers. Nontumorous liver also revealed integrated HBV‐DNA with the same or a different hybridization pattern from that observed in the tumor. To explore when integration occurs, carriers of short‐term (<2 years) or long‐term (> 8‐10 years) were evaluated. DNA extracts from percutaneous (needle) liver biopsies showed free viral DNA with no specific integration bands in short‐term carriers. In long‐term carriers, HBV‐DNA was integrated into the host genome with either a diffuse or a unique hybridization pattern. HBV‐DNA integration correlated with the duration of the carrier state and absence of virions in the serum but did not correlate with histologic evidence of chronic hepatitis. These studies suggest that integration of HBV‐DNA occurs during persistent HBV infection irrespective of liver disease and precedes development of hepatocellular carcinoma.