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ANALYSES OF HEPATITIS A VIRUS GENOME FROM PATIENTS WITH FULMINANT TYPE A HEPATITIS

暴发性甲型肝炎患者甲型肝炎病毒基因组分析

基本信息

批准号：
08457162
负责人：
YOKOSUKA Osamu
金额：
$ 3.9万
依托单位：
CHIBA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457162/
关键词：
Hepatitis A virus fulminant hepatitis mutation sequence Hepatis A 劇症肝炎塩基配列決定ウイルス変異

项目摘要

Hepatitis A still possess a considerable problem not only in underdeveloped but also in developed countries. It is not revealed why some patients progress to fulminant hepatitis A and others do not. To examine whether genomic differences of hepatitis A virus (HAV) are responsible for the clinical severity, we are analyzing whole nucleotide sequences of HAV RNA in sera from fulminant and acute hepatitis A patients. We clarified that the severity of hepatitis A appears to be associated with the substitutions near the central part of the 5' nontranslated region of HAV,because in the cases with fulminant hepatitis only a small number of substitutions were observed while in the cases with self limited acute hepatitis considerable numbers of substitutions were observed. We further determined the sequences of structural protein region of HAV.Sera from 3 fulminant and 3 acute hepatitis A patients were examined. Structural region and non-strauctural regions of HAV RNA were amplified by long reverse transcription-polymerase chain reaction (RT-PCR) devided into 3188 bp including structural protein region and 4688 bp including non-structural protein region. Each PCR product was cloned and the nucleotide sequence of structural protein region was sequenced by automated sequencer. The genotypes of examined cases were all genotype1A.There were no such obvious differeces in structural protein region as found in 5' nontranslated region between fulminant and acute hepatitis A.We are now examining the sequences of non-structural protein region of HAV.

甲型肝炎不仅在不发达国家而且在发达国家仍然存在相当大的问题。目前尚不清楚为什么有些患者会发展为暴发性甲型肝炎，而另一些患者则不会。为了检查甲型肝炎病毒 (HAV) 的基因组差异是否与临床严重程度有关，我们正在分析暴发性和急性甲型肝炎患者血清中 HAV RNA 的全核苷酸序列。我们澄清，甲型肝炎的严重程度似乎与HAV 5'非翻译区中心部分附近的替换有关，因为在暴发性肝炎病例中仅观察到少量替换，而在自限性急性肝炎病例中观察到大量替换。我们进一步测定了HAV结构蛋白区域的序列。检测了3例暴发性甲型肝炎和3例急性甲型肝炎患者的血清。采用长逆转录聚合酶链反应（RT-PCR）扩增HAV RNA的结构区和非结构区，分为3188bp（包括结构蛋白区）和4688bp（包括非结构蛋白区）。克隆每个PCR产物并通过自动测序仪对结构蛋白区域的核苷酸序列进行测序。受检病例基因型均为1A型。暴发性甲型肝炎与急性甲型肝炎5'非翻译区结构蛋白区没有明显差异。目前正在检测HAV非结构蛋白区序列。