Supplementary Material for: A MAVS/TICAM-1-Independent Interferon-Inducing Pathway Contributes to Regulation of Hepatitis B Virus Replication in the Mouse Hydrodynamic Injection Model

Toll-like receptors (TLRs) and cytoplasmic RNA sensors have been reported to be involved in the regulation of hepatitis B virus (HBV) replication, but remain controversial due to the lack of a natural infectious model. Our current study sets out to characterize aspects of the role of the innate immune system in eliminating HBV using hydrodynamic-based injection of HBV replicative plasmid and knockout mice deficient in specific pathways of the innate system. The evidence indicated that viral replication was not affected by MAVS or TICAM-1 knockout, but absence of interferon regulatory factor 3 (IRF-3) and IRF-7 transcription factors, as well as the interferon (IFN) receptor, had an adverse effect on the inhibition of HBV replication, demonstrating the dispensability of MAVS and TICAM-1 pathways in the early innate response against HBV. <i>Myd88</i>^<i>-/-</i> mice did not have a significant increase in the initial viremia, but substantial viral antigen persisted in the mice sera, a response similar to <i>Rag2</i>^<i>-/-</i> mice, suggesting that the MyD88-dependent pathway participated in evoking an adaptive immune response against the clearance of intrahepatic HBV. Taken together, we show that the RNA-sensing pathways do not participate in the regulation of HBV replication in a mouse model; meanwhile MyD88 is implicated in the HBV clearance.

已有研究表明，Toll样受体（Toll-like receptors, TLRs）与胞质RNA感受器参与调控乙型肝炎病毒（hepatitis B virus, HBV）的复制，但由于缺乏天然感染模型，相关结论仍存在争议。本研究旨在通过基于水动力注射的HBV复制性质粒转染法，结合先天免疫特定通路缺陷的敲除小鼠，阐明先天免疫系统在清除HBV过程中的作用机制。实验结果显示，MAVS或TICAM-1基因敲除对病毒复制无显著影响；而干扰素调节因子3（IRF-3）、干扰素调节因子7（IRF-7）这两种转录因子的缺失，以及干扰素（IFN）受体的缺失，均会削弱HBV复制的抑制效果，这表明MAVS与TICAM-1通路在抗HBV的早期先天免疫应答中并非必需。<i>MyD88</i>^<i>-/-</i>小鼠的初始病毒血症并未出现显著升高，但小鼠血清中仍持续存在大量病毒抗原，该表型与<i>Rag2</i>^<i>-/-</i>小鼠相似，提示MyD88依赖通路参与诱导针对肝内HBV清除的适应性免疫应答。综上，本研究证实，在该小鼠模型中，RNA感知通路并不参与HBV复制的调控；而MyD88则与HBV的清除密切相关。