Abstract
BackgroundDengue infection ranks as one of the most significant viral diseases of the globe. Currently, there is no specific vaccine or antiviral therapy for prevention or treatment. Monocytes/macrophages are the principal target cells for dengue virus and are responsible for disseminating the virus after its transmission. Dengue virus enters target cells via receptor-mediated endocytosis after the viral envelope protein E attaches to the cell surface receptor. This study aimed to investigate the effect of silencing the CD-14 associated molecule and clathrin-mediated endocytosis using siRNA on dengue virus entry into monocytes.Methodology/Principal FindingsGene expression analysis showed a significant down-regulation of the target genes (82.7%, 84.9 and 76.3% for CD-14 associated molecule, CLTC and DNM2 respectively) in transfected monocytes. The effect of silencing of target genes on dengue virus entry into monocytes was investigated by infecting silenced and non-silenced monocytes with DENV-2. Results showed a significant reduction of infected cells (85.2%), intracellular viral RNA load (73.0%), and extracellular viral RNA load (63.0%) in silenced monocytes as compared to non-silenced monocytes.Conclusions/SignificanceSilencing the cell surface receptor and clathrin mediated endocytosis using RNA interference resulted in inhibition of the dengue virus entry and subsequently multiplication of the virus in the monocytes. This might serve as a novel promising therapeutic target to attenuate dengue infection and thus reduce transmission as well as progression to severe dengue hemorrhagic fever.
Highlights
Dengue infection ranks as one of the most clinically significant and prevalent mosquito-borne viral diseases of the globe
This indicates that the interactions between dengue virus (DENV) and monocytes/ macrophages are important in the pathogenesis of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS)
This study aimed to investigate the possible usage of small interfering RNAs (siRNA) in the reduction of DENV entry and replication in human monocytes by targeting the monocytes attachment receptor and clathrin-mediated endocytosis
Summary
Dengue infection ranks as one of the most clinically significant and prevalent mosquito-borne viral diseases of the globe. Based on several observations and antibody dependent enhancement hypothesis, monocyte lineage cells are the major target for DENV [6,7,8,9] These cells are responsible for replication and dissemination of the virus after the infection from mosquito bites. DENV infected monocytes/macrophages release soluble mediators that strongly influence the biological characteristics of endothelial cells and the hematopoietic cell population. This indicates that the interactions between DENV and monocytes/ macrophages are important in the pathogenesis of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). This study aimed to investigate the effect of silencing the CD-14 associated molecule and clathrin-mediated endocytosis using siRNA on dengue virus entry into monocytes
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