PROBABLE IMPLICATION OF MUTATIONS OF THE X-OPEN-READING-FRAME IN THE ONSET OF FULMINANT-HEPATITIS-B
PROBABLE IMPLICATION OF MUTATIONS OF THE X-OPEN-READING-FRAME IN THE ONSET OF FULMINANT-HEPATITIS-B
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DOI：
10.1002/jmv.1890470304
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发表时间：
1995-11-01
影响因子：
12.7
通讯作者：
MIMA, S
中科院分区：
文献类型：
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作者：
KANEKO, M;UCHIDA, T;MIMA, S
前C区缺陷突变在暴发性B型肝炎发病中的致病作用已被提出。然而，前C区缺陷突变体并不总是引起暴发性B型肝炎，也不总是从受影响的患者中分离出来。这些发现强烈提示在暴发性肝炎前核心区以外存在一些额外的重要突变。本研究试图对7例重型B型肝炎和5例急性B型肝炎患者的B型肝炎病毒DNA的X开放阅读框进行测序。后者用作对照。由于X开放阅读框编码X蛋白，并含有核心启动子/增强子II复合物，某些关键突变可能增强或破坏B型肝炎病毒DNA的复制和表达，导致暴发性肝炎。7例重型肝炎患者中，分别为5例和5例。急性肝炎患者未发现这些替代。这些突变可能会改变X蛋白和核心启动子/增强子II复合物的功能。因此，这些突变，以及前核心缺陷型突变，可能在重型肝炎的发病机制中发挥重要作用。(C)1995 Wiley-Liss，Inc.
A pathogenic role of precore-defective mutation in the onset of fulminant hepatitis B has been suggested. However, precore-defective mutants do not always cause fulminant hepatitis B and are not always isolated from affected patients. These findings strongly suggest the presence of some additional important mutations outside the precore region in fulminant hepatitis. In the present investigation an attempt was made to sequence the X open reading frame of hepatitis B virus DNA isolated from seven patients with fulminant hepatitis B and five patients with acute hepatitis B. The latter were used as controls. Since the X open reading frame encodes the X protein and contains the core promoter/enhancer II complex, some critical mutations may enhance or disrupt the replication and expression of hepatitis B virus DNA leading to fulminant hepatitis.A C-to-T substitution was found at nucleotide (nt) 1655, an A-to-T substitution at nt 1764 and a G-to-A substitution at nt 1766 in 4, 5 and 5 patients, respectively, out of the seven with fulminant hepatitis. These substitutions were not recognized in the patients with acute hepatitis. These mutations might change the function of the X protein and core promoter/enhancer II complex. It is suggested, therefore, that these mutations, as well as the precore-defective mutation, may play an important role in the pathogenesis of fulminant hepatitis. (C) 1995 Wiley-Liss, Inc.