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Analysis of the in vitro replication phenotype of African hepatitis B virus (HBV) genotypes and subgenotypes present in Australia identifies marked differences in DNA and protein expression.
Virology ( IF 3.7 ) Pub Date : 2019-11-07 , DOI: 10.1016/j.virol.2019.11.001
E Bannister 1 , V Sozzi 2 , H Mason 2 , S Locarnini 2 , W Hardikar 3 , P A Revill 4
Affiliation  

Hepatitis B virus infection in Africa is characterised by distinct genotypes with observed differences in natural history and clinical outcomes. Replication-competent cDNA clones of African genotypes were generated from patient-derived sequences identified in African children with chronic hepatitis B infection living in Australia: A1 (wild-type and basal core promotor (BCP) mutant), D2, D6, and E, comparing the replication phenotype to an established D3 cDNA clone in a transient transfection cell culture model. All clones replicated efficiently although less than the European D3 reference clone, and demonstrated marked differences in replication capacity, highest for subgenotypes A1 and D2. The BCP mutation increased the replication levels of the A1 subgenotype compared to wild-type. Intracellular and secreted surface antigen and HBeAg protein expression also varied across genotypes. We observed differences in functional activity in the upstream regulatory region across the genotypes that may contribute to the replication and protein differences observed.

中文翻译:

对澳大利亚存在的非洲乙型肝炎病毒(HBV)基因型和亚基因型的体外复制表型进行分析,可以确定DNA和蛋白质表达的显着差异。

非洲的乙型肝炎病毒感染的特征是不同的基因型,在自然病史和临床结局方面均存在差异。具有复制能力的非洲基因型cDNA克隆是从在澳大利亚居住的患有慢性乙型肝炎的非洲儿童中鉴定的患者来源序列产生的:A1(野生型和基础核心启动子(BCP)突变体),D2,D6和E,在瞬时转染细胞培养模型中比较复制表型与已建立的D3 cDNA克隆。尽管比欧洲D3参考克隆要少,但所有克隆均能有效复制,并表现出明显的复制能力差异,亚型A1和D2最高。与野生型相比,BCP突变增加了A1亚型的复制水平。细胞内和分泌的表面抗原和HBeAg蛋白表达也随基因型而变化。我们观察到跨基因型的上游调节区域中功能活性的差异,这可能有助于观察到的复制和蛋白质差异。
更新日期:2019-11-07
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