Cholesterol biosynthesis modulation regulates dengue viral replication

被引：212

作者：

Rothwell, Christopher ^{[1
]}

LeBreton, Aude ^{[1
]}

Ng, Chuan Young ^{[2
]}

Lim, Joanne Y. H. ^{[2
]}

Liu, Wei ^{[2
]}

Vasudevan, Subhash ^{[2
]}

Labow, Mark ^{[1
]}

Gu, Feng ^{[2
]}

Gaither, L. Alex ^{[1
]}

机构：

[1] Novartis Inst Biomed Res, Cambridge, MA 02139 USA

[2] Novartis Inst Trop Dis, Singapore 138670, Singapore

来源：

VIROLOGY | 2009年 / 389卷 / 1-2期

关键词：

MVD; Mevalonate pyrophosphate decarboxylase; Dengue; Viral replication; siRNA; Host factors; Statins; CELL-LINES; VIRUS; THERAPY; IDENTIFICATION; MECHANISMS; PROTEIN; FAMILY; GROWTH; DOMAIN; FEVER;

D O I：

10.1016/j.virol.2009.03.025

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

We performed a focused siRNA screen in an A549 dengue type 2 New Guinea C subgenomic replicon cell line (Rluc-replicon) that contains a Renilla luciferase cassette. We found that siRNA mediated knock down of mevalonate diphospho decarboxylase (MVD) inhibited viral replication of the Rluc-replicon and DEN-2 NGC live virus replication in A549 cells. When the Rluc-replicon A459 cells were grown in delipidated media the replicon expression was suppressed and MVD knock down could further sensitize Renilla expression. Hymeglusin and zaragozic acid A could inhibit DEN-2 NGC live virus replication in K562 cells, while lovastatin could inhibit DEN-2 NGC live virus replication in human peripheral blood mononuclear cells. Renilla expression could be rescued in fluvastatin treated A549 Rluc-replicon cells after the addition of mevalonate, and partially restored with geranylgeranyl pyrophosphate, or farnesyl pyrophosphate. Our data suggest genetic and pharmacological modulation of cholesterol biosynthesis call regulate dengue virus replication. (c) 2009 Elsevier Inc. All rights reserved.

引用

页码：8 / 19

页数：12

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