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 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.
Umehara
Takuya
T
Department of Microbiology and Cell Biology, The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.
Sudoh
Masayuki
M
Yasui
Fumihiko
F
Matsuda
Chiho
C
Hayashi
Yukiko
Y
Chayama
Kazuaki
K
Kohara
Michinori
M
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D051379:Mice; D011092:Polyethylene Glycols / Q000494:pharmacology; D012367:RNA, Viral / Q000096:biosynthesis; D012093:Replicon / Q000187:drug effects; D051102:Serine C-Palmitoyltransferase / Q000037:antagonists & inhibitors*; D013107:Sphingolipids / Q000096:biosynthesis; D018183:Transplantation Chimera; D014758:Viral Core Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D005229:Fatty Acids, Monounsaturated; D012367:RNA, Viral; D013107:Sphingolipids; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D011092:Polyethylene Glycols; D007372:Interferons; D051102:Serine C-Palmitoyltransferase; C001996:thermozymocidin