2. Academic Validation
  3. Cholesterol biosynthesis modulation regulates dengue viral replication

Cholesterol biosynthesis modulation regulates dengue viral replication

  • Virology. 2009 Jun 20;389(1-2):8-19. doi: 10.1016/j.virol.2009.03.025.
Christopher Rothwell 1,  Aude Lebreton,  Chuan Young Ng,  Joanne Y H Lim,  Wei Liu,  Subhash Vasudevan,  Mark Labow,  Feng Gu,  L Alex Gaither
Affiliations

Affiliation

  • 1 Novartis Institutes for Biomedical Research, 250 Massachusetts Ave., Cambridge, MA 02139, USA.
PMID: 19419745 DOI: 10.1016/j.virol.2009.03.025
Abstract

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.

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