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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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22927911/?tool=EBI |
| _version_ | 1818400195554050048 |
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| 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 |
| collection | DOAJ |
| description | <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. |
| first_indexed | 2024-12-14T07:32:43Z |
| format | Article |
| id | doaj.art-b05f5f5af5774bcdaa7ad7dc47a10e35 |
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| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T07:32:43Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-b05f5f5af5774bcdaa7ad7dc47a10e352022-12-21T23:11:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4163510.1371/journal.pone.0041635Dengue virus serotype 2 blocks extracellular signal-regulated kinase and nuclear factor-κB activation to downregulate cytokine production.Tsung-Hsien ChangSiang-Ru ChenChia-Yi YuYou-Sheng LinYao-Shen ChenToru KubotaMayumi MatsuokaYi-Ling Lin<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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22927911/?tool=EBI |
| spellingShingle | 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. PLoS ONE |
| title | 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_short | 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 |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22927911/?tool=EBI |
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