Mina Thomas, Amini Bavil Olyaee Samad, Tacke Frank, Maes Piet, Van Ranst Marc, Pourkarim Mahmoud Reza
Department of Microbiology and Immunology, Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
Department of Molecular Microbiology and Immunology, Harlyne J. Norris Cancer Research Tower, Keck School of Medicine, University of Southern California, Los Angeles, USA.
Hepat Mon. 2015 Jun 23;15(6):e29477. doi: 10.5812/hepatmon.29477v2. eCollection 2015 Jun.
After five decades of Hepatitis B Virus (HBV) vaccine discovery, HBV is still a major public health problem. Due to the high genetic diversity of HBV and selective pressure of the host immune system, intra-host evolution of this virus in different clinical manifestations is a hot topic of research. HBV infection causes a range of clinical manifestations from acute to chronic infection, cirrhosis and hepatocellular carcinoma. Among all forms of HBV infection manifestations, fulminant hepatitis B infection possesses the highest fatality rate. Almost 1% of the acutely infected patients develop fulminant hepatitis B, in which the mortality rate is around 70%.
All published papers deposited in Genbank, on the topic of fulminant hepatitis were reviewed and their virological aspects were investigated. In this review, we highlight the genomic diversity of HBV reported from patients with fulminant HBV infection.
The most commonly detected diversities affect regulatory motifs of HBV in the core and S region, indicating that these alterations may convert the virus to an aggressive strain. Moreover, mutations at T-cell and B-cell epitopes located in pre-S1 and pre-S2 proteins may lead to an immune evasion of the virus, likely favoring a more severe clinical course of infection. Furthermore, point and frame shift mutations in the core region increase the viral replication of HBV and help virus to evade from immune system and guarantee its persistence.
Fulminant hepatitis B is associated with distinct mutational patterns of HBV, underlining that genomic diversity of the virus is an important factor determining its pathogenicity.
在发现乙肝病毒(HBV)疫苗五十年后,HBV仍然是一个主要的公共卫生问题。由于HBV的高度遗传多样性以及宿主免疫系统的选择压力,这种病毒在不同临床表现中的宿主内进化是一个研究热点。HBV感染会导致从急性感染到慢性感染、肝硬化和肝细胞癌等一系列临床表现。在所有形式的HBV感染表现中,暴发性乙型肝炎感染的死亡率最高。几乎1%的急性感染患者会发展为暴发性乙型肝炎,其死亡率约为70%。
对Genbank中所有已发表的关于暴发性肝炎主题的论文进行了综述,并研究了它们的病毒学方面。在本综述中,我们重点介绍了暴发性HBV感染患者中报告的HBV基因组多样性。
最常检测到的多样性影响HBV在核心区和S区的调控基序,表明这些改变可能使病毒转变为侵袭性毒株。此外,位于前S1和前S2蛋白中的T细胞和B细胞表位的突变可能导致病毒的免疫逃逸,可能有利于更严重的感染临床病程。此外,核心区的点突变和移码突变增加了HBV的病毒复制,并帮助病毒逃避免疫系统并保证其持续性。
暴发性乙型肝炎与HBV独特的突变模式相关,强调病毒的基因组多样性是决定其致病性的重要因素。