Serine palmitoyltransferase inhibitor suppresses HCV replication in a mouse model.
Serine palmitoyltransferase inhibitor suppresses HCV replication in a mouse model.
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DOI：
10.1016/j.bbrc.2006.05.085
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发表时间：
2006-07
影响因子：
3.1
通讯作者：
T. Umehara;M. Sudoh;F. Yasui;C. Matsuda;Y. Hayashi;K. Chayama;M. Kohara
中科院分区：
文献类型：
--
作者：
T. Umehara;M. Sudoh;F. Yasui;C. Matsuda;Y. Hayashi;K. Chayama;M. Kohara
丝氨酸棕榈酰基转移酶（SPT）是鞘脂生物合成途径的第一步酶。肉豆蔻素是一种SPT抑制剂，可抑制丙型肝炎病毒复制子的复制。然而，目前尚不清楚这种SPT抑制剂是否能抑制HCV在体内的复制。我们研究了肉豆杉素对HCV基因型1a或1b感染的人源化肝脏嵌合小鼠的抗HCV作用。我们给HCV感染的嵌合小鼠注射肉豆素，成功地将血清和肝脏中的HCV RNA水平降低到治疗前8天水平的1/10-1/100。此外，与聚乙二醇化干扰素联合治疗将HCV RNA水平降低到对照水平的1/1000以下。我们强烈建议抑制SPT可以减少HCV的复制，因此SPT抑制剂可能是一种治疗HCV感染的新药。
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.