Abstract：
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.
摘要：
慢性病毒性肝炎是由乙型肝炎病毒引起的，丙型肝炎病毒或丁型肝炎病毒（HBV，HCV,和HDV）。尽管复制策略不同，所有这些病毒都依赖于宿主内质网-高尔基途径的分泌，为抗病毒治疗提供潜在的宿主靶标。病毒细胞培养模型中跨膜6超家族成员2（TM6SF2）的敲减减少了感染性HCV病毒粒子的分泌，HDV病毒体和HBV亚病毒颗粒。此外，在一组乙型肝炎患者中，TM6SF2多态性（rs58542926CT/TT，导致肝脏中蛋白质错误折叠和TM6SF2减少）与血液中亚病毒颗粒浓度降低相关，补充了我们以前的工作，表明具有这种多态性的人的HCV病毒载量降低。总之,宿主蛋白TM6SF2在HBV的分泌中起关键作用，HCV和HDV，提供新型泛病毒药物治疗慢性病毒性肝炎的潜力。
