Chronic hepatitis D (CHD) is the most severe form of viral hepatitis, with rapid progression of liver-related diseases and high rates of development of hepatocellular carcinoma. The causative agent, hepatitis D virus (HDV), contains a small (approximately 1.7 kb) highly self-pairing single-strand circular RNA genome that assembles with the HDV antigen to form a ribonucleoprotein (RNP) complex. HDV depends on hepatitis B virus (HBV) envelope proteins for envelopment and de novo hepatocyte entry; however, its intracellular RNA replication is autonomous. In addition, HDV can amplify HBV independently through cell division. Cellular innate immune responses, mainly interferon (IFN) response, are crucial for controlling invading viruses, while viruses counteract these responses to favor their propagation. In contrast to HBV, HDV activates profound IFN response through the melanoma differentiation antigen 5 (MDA5) pathway. This cellular response efficiently suppresses cell-division-mediated HDV spread and, to some extent, early stages of HDV de novo infection, but only marginally impairs RNA replication in resting hepatocytes. In this review, we summarize the current knowledge on HDV structure, replication, and persistence and subsequently focus on the interplay between HDV and IFN response, including IFN activation, sensing, antiviral effects, and viral countermeasures. Finally, we discuss crosstalk with HBV.

中文翻译：

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丁型肝炎病毒与干扰素反应之间的相互作用

慢性D型肝炎（CHD）是最严重的病毒性肝炎形式，具有与肝有关的疾病快速发展和肝细胞癌高发的特点。病原体为D型肝炎病毒（HDV），包含一个小的（约1.7 kb）高度自配对的单链环状RNA基因组，该基因组与HDV抗原组装在一起形成核糖核蛋白（RNP）复合物。HDV依赖于乙型肝炎病毒（HBV）包膜蛋白进行包膜和从头进入肝细胞。但是，其细胞内RNA复制是自主的。此外，HDV可以通过细胞分裂独立地扩增HBV。细胞先天免疫应答（主要是干扰素（IFN）应答）对于控制入侵病毒至关重要，而病毒会抵消这些应答以促进其传播。与HBV相比，HDV通过黑色素瘤分化抗原5（MDA5）途径激活深刻的IFN反应。这种细胞反应有效地抑制了细胞分裂介导的HDV传播，并在一定程度上抑制了HDV从头感染的早期阶段，但仅在一定程度上损害了静息肝细胞中的RNA复制。在这篇综述中，我们总结了有关HDV结构，复制和持久性的当前知识，随后重点研究了HDV与IFN反应之间的相互作用，包括IFN激活，传感，抗病毒作用和病毒对策。最后，我们讨论与HBV的串扰。但仅在一定程度上削弱了静息肝细胞中RNA的复制。在这篇综述中，我们总结了有关HDV结构，复制和持久性的当前知识，随后重点研究了HDV与IFN反应之间的相互作用，包括IFN激活，传感，抗病毒作用和病毒对策。最后，我们讨论与HBV的串扰。但仅在一定程度上削弱了静息肝细胞中RNA的复制。在这篇综述中，我们总结了有关HDV结构，复制和持久性的当前知识，随后重点研究了HDV与IFN反应之间的相互作用，包括IFN激活，传感，抗病毒作用和病毒对策。最后，我们讨论与HBV的串扰。