U18666A, an intra-cellular cholesterol transport inhibitor, inhibits dengue virus entry and replication

被引：99

作者：

Poh, Mee Kian ^{[1
,2
,3
]}

Shui, Guanghou ^{[2
]}

Xie, Xuping ^{[1
]}

Shi, Pei-Yong ^{[1
]}

Wenk, Markus R. ^{[2
,3
]}

Gu, Feng ^{[1
]}

机构：

[1] Novartis Inst Trop Dis, Dengue Unit, 10 Biopolis Rd,Chromos 05-01, Singapore 138670, Singapore

[2] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117456, Singapore

[3] Natl Univ Singapore, Dept Biol Sci, Singapore 117456, Singapore

来源：

ANTIVIRAL RESEARCH | 2012年 / 93卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

Dengue virus; Cholesterol; Antiviral; Fatty acids; U18666A; INFECTION; PATHOGENESIS; ENHANCEMENT; DERIVATIVES; FLAVIVIRUS; ANTIBODY; PATHWAY; CELLS;

D O I：

10.1016/j.antiviral.2011.11.014

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The level of cholesterol in host cells has been shown to affect viral infection. However, it is still not understood why this level of regulation is important for successful infection. We have shown in this study that dengue virus infection was affected when the cholesterol intake in infected cells was disrupted using a cholesterol transport inhibitor, U18666A. The antiviral effect was found to result from two events: retarded viral trafficking in the cholesterol-loaded late endosomes/lysosomes and suppressed de novo sterol biosynthesis in treated infected cells. We also observed an additive antiviral effect of U18666A with C75, a fatty acid synthase inhibitor, suggesting dengue virus relies on both the host cholesterol and fatty acid biosynthesis for successful replication. (C) 2011 Elsevier B.V. All rights reserved.

引用

页码：191 / 198

页数：8

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