乙型肝炎病毒(hepatitis B virus,HBV)感染与持续性肝损伤和原发性肝细胞癌(hepatocellular carcinoma,HCC)关系密切.我国是HBV感染的高流行区,给人群带来的健康威胁和损害是关注的热点问题.HBV感染是HCC的主要病原学因素之一,但其诱导肿瘤形成潜在的分子机制依然存在争议.其中HBV的X蛋白(HBV X protein,HBx)在HBV致肝细胞损伤、诱导肝细胞恶性转化、与环境因素暴露协同诱导肝致癌作用等过程中所起的作用都是研究的焦点.HBx作为多功能调控蛋白调控大量细胞信号转导通路,包括内质网(endoplasmic reticulum,ER)应激反应,值得关注的是近几年已有文献报道HBx表达对肝细胞ER应激的诱导作用,但对调控的分子机制的认识还不明确.因此,本文综述了HBx影响肝细胞ER应激的研究进展,为HBV感染诱导肝损伤和疾病的分子机制提供线索.Persistent hepatitis B virus(HBV) infection is closely related to chronic hepatitis,cirrhosis and liver cancer.China is a country with a high prevalence of HBV infection,where the infection rate is up to 60%-70%,bringing great threat and harm to public health.What's worse is that HBV infection is the main etiology factor of primary hepatocellular carcinoma(HCC).However,the underlying mechanisms of virus-induced tumor formation remain controversial.Numerous studies indicate that HBV X protein(HBx) plays a prominent role in HBV-induced liver cell damage,hepatitis,liver fibrosis and malignant transformation,and is related to liver cancer induced by environmental exposure factors.As a multifunctional regulatory protein,HBx regulates a variety of cell signal transduction pathways,including the endoplasmic reticulum(ER) stress response.ER stress refers to the dysfunction of the ER,and misfolded or unfolded proteins gather in the ER.It is noteworthy that the expression of HBx can induce or effect ER stress,although the molecular mechanism remains unclear.This review summarizes the role of HBx in ER stress pathways,providing clues for the liver injury induced by HBV infection.国家自然科学基金资助项目,Nos.81172705,81472997,81573181 973;; 计划前期研究专项基金资助项目,No.2014CB560710;; 福建省自然科学基金资助项目,Nos.2014J01372,2015J01344~
