Chronic infections with human hepatitis viruses continue to be a major health burden worldwide. Despite the availability of an effective prophylactic vaccine against the hepatitis B virus (HBV) and of antiviral agents efficiently suppressing HBV replication, more than 250 million people are currently chronically infected with this hepatotropic DNA virus, and resolution of chronic hepatitis B (CHB) is rarely achieved. Moreover, coinfection with the hepatitis D virus (HDV), a human RNA satellite virus requiring the envelope proteins of HBV for productive viral spreading, substantially aggravates the disease course of CHB. The molecular mechanisms by which these viruses interact with each other and with the intrinsic innate responses of the hepatocytes are not fully understood. While HBV appears to avoid innate immune recognition, HDV elicits a strong enhancement of innate responses. Notwithstanding, such induction does not hamper HDV replication but contributes to liver inflammation and pathogenesis. Intriguingly, HDV appears to influence the ability of T cells to recognize infected hepatocytes by boosting antigen presentation. This review focuses on current knowledge regarding how these viruses can shape and counteract the intrinsic innate responses of the hepatocytes, thus affecting the immune system and pathogenesis. Understanding the distinct strategies of persistence that HBV and HDV have evolved is central for advancing the development of curative therapies.

人类肝炎病毒的慢性感染仍然是全世界的主要健康负担。尽管有针对乙型肝炎病毒 (HBV) 的有效预防性疫苗和有效抑制 HBV 复制的抗病毒药物，但目前仍有超过 2.5 亿人长期感染这种嗜肝 DNA 病毒，慢性乙型肝炎 (CHB) 的解决是很少达到。此外，与丁型肝炎病毒 (HDV)（一种人类 RNA 卫星病毒）共同感染，需要 HBV 的包膜蛋白才能进行有效的病毒传播，从而大大加重了 CHB 的病程。这些病毒相互作用以及与肝细胞固有的先天反应相互作用的分子机制尚不完全清楚。虽然 HBV 似乎避免了先天免疫识别，HDV 引起先天反应的强烈增强。尽管如此，这种诱导不会阻碍 HDV 复制，但会导致肝脏炎症和发病机制。有趣的是，HDV 似乎通过增强抗原呈递来影响 T 细胞识别受感染肝细胞的能力。本综述重点介绍了有关这些病毒如何塑造和抵消肝细胞固有的先天反应，从而影响免疫系统和发病机制的当前知识。了解 HBV 和 HDV 已经进化出的不同的持久性策略对于推进治愈性疗法的发展至关重要。HDV 似乎通过增强抗原呈递来影响 T 细胞识别受感染肝细胞的能力。本综述重点介绍了有关这些病毒如何塑造和抵消肝细胞固有的先天反应，从而影响免疫系统和发病机制的当前知识。了解 HBV 和 HDV 已经进化出的不同的持久性策略对于推进治愈性疗法的发展至关重要。HDV 似乎通过增强抗原呈递来影响 T 细胞识别受感染肝细胞的能力。本综述重点介绍了有关这些病毒如何塑造和抵消肝细胞固有的先天反应，从而影响免疫系统和发病机制的当前知识。了解 HBV 和 HDV 已经进化出的不同的持久性策略对于推进治愈性疗法的发展至关重要。