10月，病毒研究領域著名學術期刊Journal of Virology在線發表了中科院上海巴斯德所最新研究成果，該研究揭示了作為脂筏主要結構成分之一的鞘磷脂能夠以基因型特異性的方式激活C型肝炎病毒（HCV）1b亞型的RNA聚合酶，並且找到了其結合和激活的相關胺基酸位點。這項研究是博士研究生翁磊雲在豐田哲也研究員指導下完成的。
目前，世界上約有3%的人感染了HCV，其中主要是1b亞型，但是現在僅有的治療方法僅對不到50%的1b亞型病毒感染者有效。因此，我們亟需研製出更加高效的新型抗病毒療法。病毒RNA聚合酶是傳統的重要抗病毒藥物靶點，而很多宿主因子也通過與病毒RNA聚合酶的相互作用來調節病毒的複製和轉錄過程，因而也成為重要的抗病毒靶點。已有的研究表明，HCV的複製發生在ER衍生的脂筏結構上，並且其複製過程能夠被鞘磷脂（sphingomyelin，SM）生物合成途徑的抑制劑所抑制。
豐田哲也研究組發現的鞘磷脂對聚合酶的結合和激活作用，將可以作為研製抗病毒藥物的潛在靶點。
該研究成果得到了科技部、國家自然科學基金和中科院等相關基金的資助。（生物谷Bioon.com）
生物谷推薦英文摘要：
Journal of Virology, doi:10.1128/JVI.00638-10
Sphingomyelin Activates Hepatitis C Virus RNA Polymerase in a Genotype-Specific Manner
Leiyun Weng,1 Yuichi Hirata,2 Masaaki Arai,3 Michinori Kohara,2 Takaji Wakita,4 Koichi Watashi,4,5 Kunitada Shimotohno,5,6 Ying He,7 Jin Zhong,7 and Tetsuya Toyoda1*
Hepatitis C virus (HCV) replication and infection depend on the lipid components of the cell, and replication is inhibited by inhibitors of sphingomyelin biosynthesis. We found that sphingomyelin bound to and activated genotype 1b RNA-dependent RNA polymerase (RdRp) by enhancing its template binding activity. Sphingomyelin also bound to 1a and JFH1 (genotype 2a) RdRps but did not activate them. Sphingomyelin did not bind to or activate J6CF (2a) RdRp. The sphingomyelin binding domain (SBD) of HCV RdRp was mapped to the helix-turn-helix structure (residues 231 to 260), which was essential for sphingomyelin binding and activation. Helix structures (residues 231 to 241 and 247 to 260) are important for RdRp activation, and 238S and 248E are important for maintaining the helix structures for template binding and RdRp activation by sphingomyelin. 241Q in helix 1 and the negatively charged 244D at the apex of the turn are important for sphingomyelin binding. Both amino acids are on the surface of the RdRp molecule. The polarity of the phosphocholine of sphingomyelin is important for HCV RdRp activation. However, phosphocholine did not activate RdRp. Twenty sphingomyelin molecules activated one RdRp molecule. The biochemical effect of sphingomyelin on HCV RdRp activity was virologically confirmed by the HCV replicon system. We also found that the SBD was the lipid raft membrane localization domain of HCV NS5B because JFH1 (2a) replicon cells harboring NS5B with the mutation A242C/S244D moved to the lipid raft while the wild type did not localize there. This agreed with the myriocin sensitivity of the mutant replicon. This sphingomyelin interaction is a target for HCV infection because most HCV RdRps have 241Q.