Chronic viral hepatitis is caused by hepatitis B virus, hepatitis C virus or hepatitis D virus (HBV, HCV, and HDV). Despite different replication strategies, all these viruses rely on secretion through the host endoplasmic reticulum-Golgi pathway, providing potential host targets for antiviral therapy. Knockdown of transmembrane 6 superfamily member 2 (TM6SF2) in virus cell culture models reduced secretion of infectious HCV virions, HDV virions and HBV subviral particles. Moreover, in a cohort of people with hepatitis B a TM6SF2 polymorphism (rs58542926 CT/TT, which causes protein misfolding and reduced TM6SF2 in the liver) correlated with lower concentrations of subviral particles in blood, complementing our previous work showing decreased HCV viral load in people with this polymorphism. In conclusion, the host protein TM6SF2 plays a key role in secretion of HBV, HCV and HDV, providing the potential for novel pan-viral agents to treat people with chronic viral hepatitis.

中文翻译：

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抑制细胞因子 TM6SF2 可抑制乙型肝炎、丙型肝炎和丁型肝炎病毒的分泌途径

慢性病毒性肝炎是由乙型肝炎病毒、丙型肝炎病毒或丁型肝炎病毒（HBV、HCV 和 HDV）引起的。尽管复制策略不同，所有这些病毒都依赖于通过宿主内质网-高尔基体途径分泌，为抗病毒治疗提供了潜在的宿主靶标。病毒细胞培养模型中跨膜 6 超家族成员 2 (TM6SF2) 的敲低可减少感染性 HCV 病毒颗粒、HDV 病毒颗粒和 HBV 亚病毒颗粒的分泌。此外，在一组乙型肝炎患者中，TM6SF2 多态性（rs58542926 CT/TT，导致蛋白质错误折叠并减少肝脏中的 TM6SF2）与血液中亚病毒颗粒浓度较低相关，这补充了我们之前的研究结果，表明乙型肝炎患者中 HCV 病毒载量降低。具有这种多态性的人。总之，宿主蛋白 TM6SF2 在 HBV、HCV 和 HDV 的分泌中发挥着关键作用，为新型泛病毒药物治疗慢性病毒性肝炎提供了潜力。