Umehara Takuya, Sudoh Masayuki, Yasui Fumihiko, Matsuda Chiho, Hayashi Yukiko, Chayama Kazuaki, Kohara Michinori
Department of Microbiology and Cell Biology, The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.
Biochem Biophys Res Commun. 2006 Jul 21;346(1):67-73. doi: 10.1016/j.bbrc.2006.05.085. Epub 2006 May 24.
Serine palmitoyltransferase (SPT) is a first-step enzyme in the sphingolipid biosynthetic pathway. Myriocin is an inhibitor of SPT and suppresses replication of the hepatitis C virus (HCV) replicon. However, it is still unknown whether this SPT inhibitor suppresses HCV replication in vivo. We investigated the anti-HCV effect of myriocin against intact HCV using chimeric mice with humanized liver infected with HCV genotype 1a or 1b. We administered myriocin into HCV infected chimeric mice and succeeded in reducing the HCV RNA levels in serum and liver to 1/10-1/100 of the levels prior to the 8 day treatment. Furthermore, combined treatment with pegylated interferon reduced the HCV RNA levels to less than 1/1000 of the control levels. We strongly suggest that suppression of SPT reduces HCV replication, and therefore that the SPT inhibitor is potentially a novel drug in the treatment of HCV infection.
丝氨酸棕榈酰转移酶（SPT）是鞘脂生物合成途径中的第一步酶。麦角硫因是SPT的抑制剂，可抑制丙型肝炎病毒（HCV）复制子的复制。然而，这种SPT抑制剂是否能在体内抑制HCV复制仍不清楚。我们使用感染了HCV 1a或1b基因型的人源化肝脏嵌合小鼠，研究了麦角硫因对完整HCV的抗HCV作用。我们将麦角硫因给予感染HCV的嵌合小鼠，并成功将血清和肝脏中的HCV RNA水平降低至8天治疗前水平的1/10至1/100。此外，聚乙二醇化干扰素联合治疗可将HCV RNA水平降低至对照水平的1/1000以下。我们强烈建议抑制SPT可减少HCV复制，因此SPT抑制剂可能是治疗HCV感染的新型药物。
