Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, China.
Imaging Department, The Second Affiliated Hospital of Shandong First Medical University, Taian, China.
Front Immunol. 2022 Feb 17;13:829923. doi: 10.3389/fimmu.2022.829923. eCollection 2022.
As a small DNA virus, hepatitis B virus (HBV) plays a pivotal role in the development of various liver diseases, including hepatitis, cirrhosis, and liver cancer. Among the molecules encoded by this virus, the HBV X protein (HBX) is a viral transactivator that plays a vital role in HBV replication and virus-associated diseases. Accumulating evidence so far indicates that pattern recognition receptors (PRRs) are at the front-line of the host defense responses to restrict the virus by inducing the expression of interferons and various inflammatory factors. However, depending on HBX, the virus can control PRR signaling by modulating the expression and activity of essential molecules involved in the toll-like receptor (TLR), retinoic acid inducible gene I (RIG-I)-like receptor (RLR), and NOD-like receptor (NLR) signaling pathways, to not only facilitate HBV replication, but also promote the development of viral diseases. In this review, we provide an overview of the mechanisms that are linked to the regulation of PRR signaling mediated by HBX to inhibit innate immunity, regulation of viral propagation, virus-induced inflammation, and hepatocarcinogenesis. Given the importance of PRRs in the control of HBV replication, we propose that a comprehensive understanding of the modulation of cellular factors involved in PRR signaling induced by the viral protein may open new avenues for the treatment of HBV infection.
作为一种小型 DNA 病毒，乙型肝炎病毒（HBV）在各种肝脏疾病的发展中起着关键作用，包括肝炎、肝硬化和肝癌。在该病毒编码的分子中，HBV X 蛋白（HBX）是一种病毒转录激活因子，在 HBV 复制和病毒相关疾病中发挥重要作用。到目前为止，越来越多的证据表明，模式识别受体（PRRs）是宿主防御反应的第一线，通过诱导干扰素和各种炎症因子的表达来限制病毒。然而，根据 HBX，病毒可以通过调节参与 Toll 样受体（TLR）、视黄酸诱导基因 I（RIG-I）样受体（RLR）和 NOD 样受体（NLR）信号通路的必需分子的表达和活性来控制 PRR 信号，不仅促进 HBV 复制，还促进病毒疾病的发展。在这篇综述中，我们概述了与 HBX 介导的 PRR 信号调节相关的机制，这些机制可抑制先天免疫、调节病毒增殖、病毒诱导的炎症和肝癌发生。鉴于 PRRs 在控制 HBV 复制中的重要性，我们提出，全面了解病毒蛋白诱导的 PRR 信号中细胞因子的调节可能为治疗 HBV 感染开辟新途径。
