重型肝炎
肝细胞癌
乙型肝炎病毒
生物
肝硬化
病毒
病毒学
免疫系统
基因组不稳定性
突变
免疫学
基因
医学
癌症研究
遗传学
DNA损伤
DNA
胃肠病学
作者
Teresa Pollicino,Irene Cacciola,Francesca Saffioti,Giovanni Raimondo
标识
DOI:10.1016/j.jhep.2014.04.041
摘要
The emergence and takeover of hepatitis B virus (HBV) variants carrying mutation(s) in the preS/S genomic region is a fairly frequent event that may occur spontaneously or may be the consequence of immunoprophylaxis or antiviral treatments. Selection of preS/S mutants may have relevant pathobiological and clinical implications. Both experimental data and studies in humans show that several specific mutations in the preS/S gene may induce an imbalance in the synthesis of the surface proteins and their consequent retention within the endoplasmic reticulum (ER) of the hepatocytes. The accumulation of mutated surface proteins may cause ER stress with the consequent induction of oxidative DNA damage and genomic instability. Viral mutants with antigenically modified surface antigen may be potentially infectious to immune-prophylaxed patients and may account for cases of occult HBV infection. In addition, preS/S variants were reported to be associated with cases of fulminant hepatitis as well as of fibrosing cholestatic hepatitis, and they are associated with cirrhosis and hepatocellular carcinoma development.
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