Subcellular localisation of the X protein in HBV infected hepatocytes
Subcellular localisation of the X protein in HBV infected hepatocytes
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DOI：
10.1002/jmv.1067
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发表时间：
2001-08-01
影响因子：
12.7
通讯作者：
McGarvey, MJ
中科院分区：
文献类型：
--
作者：
Hoare, J;Henkler, F;McGarvey, MJ
B型肝炎病毒X蛋白（HBx）是一种多功能蛋白，主要通过作为病毒和多种宿主细胞基因的转录反式激活因子发挥其作用。HBx被认为是维持病毒复制所必需的，并与慢性感染B型肝炎病毒的患者发生肝细胞癌有关。关于其功能机制知之甚少，尽管已经在体外证明了与几种核蛋白和胞质蛋白的相互作用，但对于HBx在感染肝细胞中的定位没有明确的共识。在这项研究中，使用抗HBx兔多克隆抗血清在人肝活检中检查HBx的表达和细胞内分布。在慢性HBV感染患者的样本中检出HBx的比例很高（69%）。HBx的检测与肝硬化的存在和血清e抗原的存在相关。HBx主要在细胞质中检测到;然而，在高达20%的阳性染色肝细胞的细胞核中也发现了HBx，无论是仅在细胞核中还是在同一细胞内的细胞核和细胞质中均存在。此外，HBx的细胞内分布进行了分析，在转染Huh-7细胞通过共聚焦显微镜，使用单克隆抗体16 F1。在这些实验中，在显著比例的HBx表达细胞中确认了实质性核检测。这些数据表明核HBx的高功能意义，与反式激活可能涉及与核蛋白相互作用的概念一致。J. Med. Virol. 64：419-426，2001. (C)2001 Wiley-Liss，Inc.
Hepatitis B virus X protein (HBx) is a multi-functional protein that exerts its effects primarily by acting as a transcriptional transactivator of viral and multiple host cell genes. HBx is thought to be essential for maintaining viral replication and has been implicated in the development of hepatocellular carcinoma in patients chronically infected with hepatitis B virus. Very little is known about its functional mechanisms and although interactions with several nuclear and cytoplasmic proteins have been demonstrated in vitro, there is no clear consensus as to where HBx localises in infected hepatocytes, In this study, the expression and intracellular distribution of HBx were examined in human liver biopsies using an anti-HBx rabbit polyclonal antiserum. HBx was detected in a high proportion (69%) of samples from patients with chronic HBV infection. Detection of HBx correlated with the absence of cirrhosis and the presence of serum e-antigen. HBx was detected predominantly in the cytoplasm; however, it was also found in the nuclei of up to 20% of positively stained hepatocytes, either exclusively nuclear or localised both in the nucleus and cytoplasm within the same cell. Furthermore, the intracellular distribution of HBx was analysed in transfected Huh-7 cells by confocal microscopy, using the monoclonal antibody 16F1. In these experiments, a substantial nuclear detection was confirmed in a significant proportion of HBx expressing cells. The data indicate a high functional significance of nuclear HBx, consistent with the concept that transactivation may involve interactions with nuclear proteins. J. Med. Virol. 64:419-426, 2001. (C) 2001 Wiley-Liss, Inc.