摘要
乙型肝炎病毒(hepatitis B virus,HBV)慢性感染是我国人群肝细胞癌(hepatocellular carcinoma,HCC)的最主要病因。在慢性感染状态到HCC的恶性转化过程中,HBV在宿主免疫微环境下被动地选择出适合病毒生存的相关突变。这些突变的产生一方面可以帮助病毒获得逃避免疫能力,使其更加适应肝脏炎症微环境;另一方面可以显著促进HCC发生、发展,很快导致携带病毒宿主-患者的死亡而终止病毒的进化过程。在HBV的母婴传播过程中,野生型HBV,而非具有癌症相关变异的HBV,更加容易感染新生儿肝细胞。其中少部分野生型HBV在长达50年以上的慢性感染过程中逐渐进化成致癌能力较强的变异型HBV,但是这种变异难以传递下去。在这些研究基础上,我们提出了HBV致癌"末路变异"的假说。本文对该假说的来源、解释及应用进行了总结。
Chronic infection with hepatitis B virus（HBV）is the most common cause of hepatocellular carcinoma（HCC）in China.During malignant transformation from HBV infection to different states of hepatocarcinogenesis,the survival-facilitating HBV mutations are passively selected under the host immune pressure.These mutations help HBV escape from the immune eradication,making HBV more adaptable to hepatic inflammatory microenvironment.On the other hand,these HBV mutations can promote HCC development and cause the death of HBV-carrying hosts,thus terminating the evolutionary process of HBV.In the process of mother-tochild transmission,wild-type HBV particles,rather than the mutated counterparts,are more likely to infect hepatocytes of the newborns.In the subsequent chronic infection for 50 years or longer,small percentage of wild-type HBV particles evolve gradually into ＂ mutated＂ ones with increasing carcinogenic potential.However,these mutations are less likely to be transmitted into next generations.Based on these studies,we present hypothesis of ＂dead-end＂ evolution of HBV during HBV-induced hepatocarcinogenesis.Here,we summarize the rational,interpretation,and application of this scientific hypothesis.
出处
《中国病毒病杂志》
CAS
2016年第6期432-437,共6页
Chinese Journal of Viral Diseases
基金
国家重点基础研究发展计划(973计划)(2015CB554006)
国家自然科学基金重大研究计划集成项目(91529305)
国家自然科学基金重点国际(地区)合作项目(81520108021)
国家自然科学基金面上项目(81673250)
关键词
乙型肝炎病毒
基因突变
进化
免疫遗传
肝细胞癌
Hepatitis B virus
Mutations
Evolution
Immune genetics
Hepatocellular carcinoma
