Cholesterol biosynthesis modulation regulates dengue viral replication
| Autor: | Feng Gu, L. Alex Gaither, Chuan Young Ng, Mark Labow, Wei Liu, Christopher Rothwell, Subhash G. Vasudevan, Joanne Y.H. Lim, Aude LeBreton |
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| Rok vydání: | 2009 |
| Předmět: |
Indoles
Geranylgeranyl pyrophosphate Carboxy-Lyases viruses Farnesyl pyrophosphate Mevalonic Acid Dengue virus Biology Virus Replication medicine.disease_cause Fatty Acids Monounsaturated Dengue chemistry.chemical_compound Polyisoprenyl Phosphates Virology Viral replication medicine Humans Replicon RNA Small Interfering Fluvastatin A549 cell Mevalonate pyrophosphate decarboxylase Statins Tricarboxylic Acids Dengue Virus Bridged Bicyclo Compounds Heterocyclic Molecular biology Cholesterol chemistry Cell culture Gene Knockdown Techniques siRNA MVD Host factors Hydroxymethylglutaryl-CoA Reductase Inhibitors K562 Cells Sesquiterpenes K562 cells |
| Zdroj: | Virology. 389(1-2):8-19 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2009.03.025 |
| Popis: | 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 can regulate dengue virus replication. |
| Databáze: | OpenAIRE |
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