Zou Zhi-Qiang, Wang Li, Wang Kai, Yu Ji-Guang
Zhi-Qiang Zou, Li Wang, Ji-Guang Yu, Infectious Disease Hospital of Yantai, Yantai 264001, Shandong Province, China.
World J Hepatol. 2016 Jun 18;8(17):716-25. doi: 10.4254/wjh.v8.i17.716.
Approximately 400 million people are chronically infected with hepatitis B virus (HBV) globally despite the widespread immunization of HBV vaccine and the development of antiviral therapies. The immunopathogenesis of HBV infection is initiated and driven by complexed interactions between the host immune system and the virus. Host immune responses to viral particles and proteins are regarded as the main determinants of viral clearance or persistent infection and hepatocyte injury. Innate immune system is the first defending line of host preventing from virus invasion. It is acknowledged that HBV has developed active tactics to escape innate immune recognition or actively interfere with innate immune signaling pathways and induce immunosuppression, which favor their replication. HBV reduces the expression of pattern-recognition receptors in the innate immune cells in humans. Also, HBV may interrupt different parts of antiviral signaling pathways, leading to the reduced production of antiviral cytokines such as interferons that contribute to HBV immunopathogenesis. A full comprehension of the mechanisms as to how HBV inactivates various elements of the innate immune response to initiate and maintain a persistent infection can be helpful in designing new immunotherapeutic methods for preventing and eradicating the virus. In this review, we aimed to summarize different branches the innate immune targeted by HBV infection. The review paper provides evidence that multiple components of immune responses should be activated in combination with antiviral therapy to disrupt the tolerance to HBV for eliminating HBV infection.
尽管乙肝病毒(HBV)疫苗已广泛接种且抗病毒治疗也有所发展,但全球仍有约4亿人慢性感染乙肝病毒。HBV感染的免疫发病机制由宿主免疫系统与病毒之间复杂的相互作用引发并驱动。宿主对病毒颗粒和蛋白质的免疫反应被视为病毒清除或持续感染以及肝细胞损伤的主要决定因素。固有免疫系统是宿主防止病毒入侵的第一道防线。人们已知HBV已形成主动策略来逃避固有免疫识别或积极干扰固有免疫信号通路并诱导免疫抑制,这有利于其复制。HBV降低人类固有免疫细胞中模式识别受体的表达。此外,HBV可能会中断抗病毒信号通路的不同部分,导致抗病毒细胞因子(如干扰素)的产生减少,而干扰素有助于HBV的免疫发病机制。全面了解HBV如何使固有免疫反应的各种元件失活以引发并维持持续感染的机制,有助于设计预防和根除该病毒的新免疫治疗方法。在本综述中,我们旨在总结HBV感染所靶向的固有免疫的不同分支。该综述文章提供的证据表明,应结合抗病毒治疗激活免疫反应的多个组分,以打破对HBV的耐受性,从而消除HBV感染。