Dengue virus serotype 2 blocks extracellular signal-regulated kinase and nuclear factor-κB activation to downregulate cytokine production.

<h4>Background</h4>Dengue virus (DENV) infection is the most common mosquito-borne viral disease threatening human health around the world. Type I interferon (IFN) and cytokine production are crucial in the innate immune system. We previously reported that DENV serotype 2 (DENV-2) induce...

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Autores principales: Tsung-Hsien Chang, Siang-Ru Chen, Chia-Yi Yu, You-Sheng Lin, Yao-Shen Chen, Toru Kubota, Mayumi Matsuoka, Yi-Ling Lin
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2012
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Acceso en línea:https://doaj.org/article/b05f5f5af5774bcdaa7ad7dc47a10e35
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Sumario:<h4>Background</h4>Dengue virus (DENV) infection is the most common mosquito-borne viral disease threatening human health around the world. Type I interferon (IFN) and cytokine production are crucial in the innate immune system. We previously reported that DENV serotype 2 (DENV-2) induced low levels of interferon regulatory factor 3 and NF-κB activation, thus leading to reduced production of IFN-β in the early phase of infection. Here, we determined whether DENV infection not only hampers type I IFN activation but also cytokine production triggered by Toll-like receptor (TLR) signaling.<h4>Methodology/principal findings</h4>We used quantitative RT-PCR and found that only low levels of IFN-β and inflammatory cytokines such as interleukin 10 (IL-10), IL-12 and tumor necrosis factor α (TNFα) mRNA were detected in DENV-2-infected bone-marrow-derived dendritic cells. Furthermore, DENV-2 infection repressed cytokine production triggered by TLR signaling. To elucidate the molecular mechanisms underlying this suppression event, we measured NF-κB activation by p65 nuclear translocation and luciferase reporter assay and found that NF-κB activation triggered by TLR ligands was blocked by DENV-2 infection. As well, extracellular signal-regulated kinase (ERK) activity was suppressed by DENV-2 infection.<h4>Conclusions/significance</h4>To downregulate the host innate immunity, DENV-2 by itself is a weak inducer of type I IFN and cytokines, furthermore DENV-2 can also block the TLR-triggered ERK-NF-κB activation and cytokine production.