Host sphingolipid biosynthesis is a promising therapeutic target for the inhibition of hepatitis B virus replication
Host sphingolipid biosynthesis is a promising therapeutic target for the inhibition of hepatitis B virus replication
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DOI：
10.1002/jmv.21970
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发表时间：
2011-04
影响因子：
12.7
通讯作者：
Kanako Tatematsu;Yasuhito Tanaka;M. Sugiyama;M. Sudoh;M. Mizokami
中科院分区：
文献类型：
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作者：
Kanako Tatematsu;Yasuhito Tanaka;M. Sugiyama;M. Sudoh;M. Mizokami
丝氨酸棕榈酰基转移酶(SPT)催化鞘磷脂生物合成的第一步。Myriocin抑制SPT，体外和体内研究表明，它能抑制丙型肝炎病毒(HCV)的复制。然而，它对乙肝病毒(HBV)复制的影响尚不清楚。本研究用麦角菌素成功地降低了Huh7细胞培养上清液中的HBVDNA水平，发现麦角菌素的半数抑制浓度约为5µM，并将麦角菌素和/或聚乙二醇化干扰素(PEG化干扰素)作用于嵌合小鼠2周，观察这些化合物对HBVDNA水平的影响。单独应用霉菌素不能有效地降低HBVDNA水平，而单独使用聚乙二醇化干扰素可将DNA水平降低到对照水平的十分之一。霉菌素与聚乙二醇化干扰素联合应用，可使乙肝病毒水平降至对照水平的1/1000，并使乙肝病毒表面抗原和核心蛋白水平降低1.0log。在其他治疗组中没有观察到后一种效果。综上所述，杨梅菌素与聚乙二醇化干扰素联合应用可协同抑制体内的乙肝病毒复制，而不会产生肝毒性。J.Med.维罗尔。2011年，83：587-593。©2011 Wiley-Liss，Inc.
Serine palmitoyltransferase (SPT) catalyzes the first step in the sphingolipid biosynthetic pathway. Myriocin inhibits SPT and was shown to suppress the replication of hepatitis C virus (HCV) in vitro and in vivo. However, its effect on hepatitis B virus (HBV) replication is unknown. In this study, the HBV DNA levels in HuH7 cell culture supernatants were lowered successfully by using myriocin and it was found that the 50% inhibitory concentration of myriocin is approximately 5 µM. Myriocin and/or pegylated interferon (PEG‐IFN) were also administered to chimeric mice for 2 weeks and the effects of these compounds on HBV DNA levels were determined. Myriocin alone did not reduce effectively the HBV DNA levels, whereas PEG‐IFN alone reduced the DNA levels to 1/10th of the control levels. The combination of myriocin with PEG‐IFN reduced the HBV levels to about 1/1,000th of the control levels and induced a 1.0 log reduction in the levels of the HBV surface antigen and core protein. This latter effect was not observed in the other treatment groups. In conclusion, the combination of myriocin with PEG‐IFN represses synergistically HBV replication in vivo without inducing hepatotoxicity. J. Med. Virol. 83:587–593, 2011. © 2011 Wiley‐Liss, Inc.