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

ABSTRACT: BACKGROUND: 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-?B activation, thus leading to reduced production of IFN-? 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. METHODOLOGY/PRINCIPAL FINDINGS: We used quantitative RT-PCR and found that only low levels of IFN-? and inflammatory cytokines such as interleukin 10 (IL-10), IL-12 and tumor necrosis factor ? (TNF?) 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-?B activation by p65 nuclear translocation and luciferase reporter assay and found that NF-?B 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. CONCLUSIONS/SIGNIFICANCE: 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-?B activation and cytokine production.

SUBMITTER: Chang TH 

PROVIDER: S-EPMC3425550 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature