研究动态
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乙型肝炎病毒和家猫肝炎病毒通过核苷酸转运体(NTCP)作为共同的入侵受体的保守使用。

Conserved use of the sodium/bile acid cotransporter (NTCP) as an entry receptor by hepatitis B virus and domestic cat hepadnavirus.

发表日期:2023 Aug 01
作者: Maya Shofa, Akiho Ohkawa, Yasuyuki Kaneko, Akatsuki Saito
来源: ANTIVIRAL RESEARCH

摘要:

包括乙型肝炎病毒(HBV)在内的正单层肝炎病毒属可以引起人类慢性肝炎和肝癌。最近,发现了一种新的猫肝炎病毒,被命名为家猫肝炎病毒(DCH),其与HBV基因相似。DCH感染与猫慢性肝炎相关,显示与HBV发病机制相似,并具有作为HBV研究新型动物模型的潜力。已证实HBV利用钠/胆酸共转运体(NTCP)作为主要的细胞进入受体,但DCH的相应受体尚不清楚。在本研究中,我们尝试确定DCH的进入受体。HBV和DCH衍生的preS1肽段可以有效结合人和猫的NTCP,而NTCP蛋白的158位氨基酸残基决定了DCH preS1肽段的物种特异性结合。HBV进入抑制剂Myrcludex B可以阻断DCH preS1肽段的结合。因此,DCH和HBV可能共享细胞进入分子,可能存在种间传播的可能性。此外,我们的研究表明DCH可用作HBV研究的新型模型。版权所有 © 2023,由Elsevier B.V.出版。
The Orthohepadnavirus genus includes hepatitis B virus (HBV) that can cause chronic hepatitis and hepatocarcinoma in humans. Recently, a novel hepadnavirus in cats, domestic cat hepadnavirus (DCH), was identified that is genetically close to HBV. DCH infection is associated with chronic hepatitis in cats, suggesting a similarity with HBV pathogenesis and the potential to use DCH as a novel animal model for HBV research. HBV is shown to use the sodium/bile acid cotransporter (NTCP) as a major cell entry receptor, but the equivalent receptor for DCH remains unknown. Here we sought to identify the entry receptor for DCH. HBV- and DCH-derived preS1 peptides efficiently bound to both human and cat NTCPs, and residue 158 of NTCP proteins determined the species-specific binding of the DCH preS1 peptide. Myrcludex B, an HBV entry inhibitor, blocked the binding of the DCH preS1 peptide. Thus, DCH and HBV may share cell entry molecules, suggesting a possibility of inter-species transmission. Furthermore, our study suggests that DHC can be useful as a novel model for HBV research.Copyright © 2023. Published by Elsevier B.V.