Serine palmitoyltransferase inhibitor suppresses HCV replication in a mouse model

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 invest...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2006-07, Vol.346 (1), p.67-73
Main Authors: Umehara, Takuya, Sudoh, Masayuki, Yasui, Fumihiko, Matsuda, Chiho, Hayashi, Yukiko, Chayama, Kazuaki, Kohara, Michinori
Format: Article
Language:English
Subjects:
Animals
Antiviral Agents - pharmacology
Cell Line
Chimeric mice with humanized liver
Enzyme Inhibitors - therapeutic use
Fatty Acids, Monounsaturated - pharmacology
HCV
Hepacivirus - drug effects
Hepacivirus - physiology
Hepatitis C virus
Hepatitis C, Chronic - drug therapy
Humans
Interferons - pharmacology
Lipid raft
Mice
Myriocin
Polyethylene Glycols - pharmacology
Replicon - drug effects
RNA, Viral - biosynthesis
Serine C-Palmitoyltransferase - antagonists & inhibitors
Serine palmitoyltransferase
Sphingolipids - biosynthesis
Transplantation Chimera
Viral Core Proteins - biosynthesis
Virus Replication - drug effects
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2006.05.085