Victorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital, Peter Doherty Institute of Infection and Immunity, 792 Elizabeth St, Melbourne, 3000 Victoria, Australia.
Key Laboratory of Medical Molecular Virology, School of Basic and Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
Virology. 2018 Jun;519:190-196. doi: 10.1016/j.virol.2018.04.015. Epub 2018 May 4.
Hepatitis B virus (HBV) exists as 9 major genotypes and multiple subtypes, many of which exhibit differences in pathogenicity and treatment response. Genotype H identified in Central America is associated with low incidence of liver disease and HCC, but higher incidence of occult HBV (low level HBV DNA positivity, HBsAg negative). The replication phenotype of genotype H associated with less severe forms of liver disease is unknown. We hypothesized that the reduced pathogenesis associated with this genotype may be due to by lower rates of viral replication and/or secretion compared to other characterised strains. We used transient transfection and infection cell culture models to characterise the replication phenotype, compared to our D3 reference strain. Genotype H exhibited reduced viral replication and altered envelope protein expression compared to genotype D, with functional studies showing that low replication was in part likely due to sequence differences in the major transcriptional regulatory region.
乙型肝炎病毒(HBV)存在 9 种主要基因型和多种亚型,其中许多在致病性和治疗反应方面存在差异。在中美洲发现的基因型 H 与肝病和 HCC 的发病率较低相关,但隐匿性 HBV(低水平 HBV DNA 阳性,HBsAg 阴性)的发病率较高。与肝病较轻形式相关的基因型 H 的复制表型尚不清楚。我们假设与这种基因型相关的较低发病机制可能是由于与其他特征菌株相比,病毒复制和/或分泌率较低。我们使用瞬时转染和感染细胞培养模型来表征复制表型,与我们的 D3 参考株进行比较。与基因型 D 相比,基因型 H 表现出病毒复制减少和包膜蛋白表达改变,功能研究表明,低复制部分可能是由于主要转录调控区的序列差异所致。