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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oai:doaj.org-article:b05f5f5af5774bcdaa7ad7dc47a10e352021-11-18T07:08:02ZDengue virus serotype 2 blocks extracellular signal-regulated kinase and nuclear factor-κB activation to downregulate cytokine production.1932-620310.1371/journal.pone.0041635https://doaj.org/article/b05f5f5af5774bcdaa7ad7dc47a10e352012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22927911/?tool=EBIhttps://doaj.org/toc/1932-6203<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.Tsung-Hsien ChangSiang-Ru ChenChia-Yi YuYou-Sheng LinYao-Shen ChenToru KubotaMayumi MatsuokaYi-Ling LinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e41635 (2012) |
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Medicine R Science Q Tsung-Hsien Chang Siang-Ru Chen Chia-Yi Yu You-Sheng Lin Yao-Shen Chen Toru Kubota Mayumi Matsuoka Yi-Ling Lin Dengue virus serotype 2 blocks extracellular signal-regulated kinase and nuclear factor-κB activation to downregulate cytokine production. |
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<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. |
format |
article |
author |
Tsung-Hsien Chang Siang-Ru Chen Chia-Yi Yu You-Sheng Lin Yao-Shen Chen Toru Kubota Mayumi Matsuoka Yi-Ling Lin |
author_facet |
Tsung-Hsien Chang Siang-Ru Chen Chia-Yi Yu You-Sheng Lin Yao-Shen Chen Toru Kubota Mayumi Matsuoka Yi-Ling Lin |
author_sort |
Tsung-Hsien Chang |
title |
Dengue virus serotype 2 blocks extracellular signal-regulated kinase and nuclear factor-κB activation to downregulate cytokine production. |
title_short |
Dengue virus serotype 2 blocks extracellular signal-regulated kinase and nuclear factor-κB activation to downregulate cytokine production. |
title_full |
Dengue virus serotype 2 blocks extracellular signal-regulated kinase and nuclear factor-κB activation to downregulate cytokine production. |
title_fullStr |
Dengue virus serotype 2 blocks extracellular signal-regulated kinase and nuclear factor-κB activation to downregulate cytokine production. |
title_full_unstemmed |
Dengue virus serotype 2 blocks extracellular signal-regulated kinase and nuclear factor-κB activation to downregulate cytokine production. |
title_sort |
dengue virus serotype 2 blocks extracellular signal-regulated kinase and nuclear factor-κb activation to downregulate cytokine production. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2012 |
url |
https://doaj.org/article/b05f5f5af5774bcdaa7ad7dc47a10e35 |
work_keys_str_mv |
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