The specific SM molecular species that these endogenous SM species interacted with HCV nonstructural 5B polymerase to enhance viral replication

脂质是病毒生命周期中影响宿主-病原体相互作用的关键组分。在这项研究中，我们研究了HCV感染对鞘脂代谢的影响，特别是对内源性SM水平，以及HCV复制和内源性SM分子种类之间的关系。我们证明，HCV诱导鞘磷脂（SM）酶编码基因的表达。我们观察到相关的增加，总的和个人的鞘脂分子种类，在人类肝细胞和耐洗涤剂膜（DRM）部分，其中HCV复制评估。SGMS-1表达与HCV复制密切相关。用亲肝丝氨酸棕榈酰转移酶抑制剂NA 808抑制鞘脂生物合成，抑制HCV-RNA的产生，同时也干扰鞘脂代谢。此外，我们确定了特定的SM分子种类，包括DRM部分，并证明这些内源性SM物种与HCV非结构性5 B聚合酶相互作用，以增强病毒复制。我们的研究结果表明，HCV改变鞘脂代谢，以促进病毒复制，提供新的见解形成的HCV复制复合物和参与宿主脂质在HCV的生命周期。

Lipids are key components in the viral life cycle that affect host-pathogen interactions. In this study, we investigated the effect of HCV infection on sphingolipid metabolism, especially on endogenous SM levels, and the relationship between HCV replication and endogenous SM molecular species. We demonstrated that HCV induces the expression of the genes encoding sphingomyelin(SM) synthases. We observed associated increases of both total and individual sphingolipid molecular species, as assessed in human hepatocytes and in the detergent-resistant membrane(DRM) fraction in which HCV replicates. SGMS-1 expression had a strong correlation with HCV replication. Inhibition of sphingolipid biosynthesis with a hepatotropic serine palmitoyltransferase inhibitor, NA808, suppressed HCV-RNA production while also interfering with sphingolipid metabolism. Further, we identified the specific SM molecular species that comprise the DRM fraction and demonstrated that these endogenous SM species interacted with HCV nonstructural 5B polymerase to enhance viral replication. Our results reveal that HCV alters sphingolipid metabolism to promote viral replication, providing new insights into the formation of the HCV replication complex and the involvement of host lipids in the HCV life cycle.