Uchida T, Saitoh T, Shinzawa H
Department of Pathology, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan.
Pathol Int. 1997 Apr;47(4):183-93. doi: 10.1111/j.1440-1827.1997.tb04479.x.
Nucleotide (nt) sequences of the X region of more than 130 hepatitis B virus (HBV) isolates were determined and derived from patients with a variety of clinical features. Correlation of nt substitutions with clinicopathological characteristics was attempted. The X region (465nt) is crucial for the replication and expression of HBV because the X protein transactivates the HBV genes and this region contains the core promoter, enhancer II, and two direct repeats. There are several mutational hotspots, some of which seem to relate to immunological epitopes of the X protein. Two kinds of mutations which have important clinical significances were found. One is an 8-nt deletion between nt 1770 and 1777, which truncates 20 amino acids from the carboxyl terminus of the X protein. This deletion leads to the suppression of replication and expression of HBV DNA, resulting in immunoserological marker (HBsAg) negativity. This silent HBV infection is responsible for the majority of non-A to non-E hepatitis. The other mutation substituting T for C (nt 1655), T for A (nt 1764) and A for G (nt 1766) seems to relate to fulminant hepatitis. Further sequencing studies and in vitro mutagenesis experiments will clarify the significance of other mutations of the X region.
测定了130多株乙型肝炎病毒（HBV）分离株X区域的核苷酸（nt）序列，这些分离株来源于具有各种临床特征的患者。尝试将nt替换与临床病理特征进行关联分析。X区域（465nt）对HBV的复制和表达至关重要，因为X蛋白可反式激活HBV基因，且该区域包含核心启动子、增强子II和两个直接重复序列。存在几个突变热点，其中一些似乎与X蛋白的免疫表位有关。发现了两种具有重要临床意义的突变。一种是nt 1770和1777之间的8nt缺失，该缺失从X蛋白的羧基末端截短了20个氨基酸。这种缺失导致HBV DNA复制和表达受到抑制，导致免疫血清学标志物（HBsAg）呈阴性。这种隐匿性HBV感染是大多数非甲至非戊型肝炎的病因。另一种突变是C被T替换（nt 1655）、A被T替换（nt 1764）以及G被A替换（nt 1766），这似乎与暴发性肝炎有关。进一步的测序研究和体外诱变实验将阐明X区域其他突变的意义。
