Dengue virus (DENV) antibody-dependent enhancement of infection upregulates the production of anti-inflammatory cytokines, but suppresses anti-DENV free radical and pro-inflammatory cytokine production, in THP-1 cells
Dengue virus (DENV) antibody-dependent enhancement of infection upregulates the production of anti-inflammatory cytokines, but suppresses anti-DENV free radical and pro-inflammatory cytokine production, in THP-1 cells
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DOI：
10.1099/vir.0.82537-0
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发表时间：
2007-02-01
影响因子：
3.8
通讯作者：
Ubol, Sukathida
中科院分区：
文献类型：
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作者：
Chareonsirisuthigul, Takol;Kalayanarooj, Siripen;Ubol, Sukathida
登革出血热和登革休克综合征的免疫发病机制被认为是由多种宿主因素介导的。增强抗体是关键的调节分子之一。这些抗体通过抗体依赖性增强（ADE）感染，能够促进登革热病毒（DENV）在携带fc的宿主细胞中生长。ade增强DENV产生的机制被认为是通过增加感染细胞质量介导的。在本工作中，进一步探讨了AIDE感染的影响，重点关注AIDE感染的进入后事件。据推测，与DENV感染相比，AIDE感染的病毒产量更高可能是由于这种感染途径抑制关键抗病毒分子的能力。因此，我们研究了AIDE感染对白细胞介素-1 - 2 （IL-12）、γ干扰素（ifn - γ）、肿瘤坏死因子α (tnf - α)、IL-6和IL-10等促炎性和抗炎性细胞因子的影响，发现通过Fc受体介导的途径感染DENV能够抑制L-12、ifn - γ和tnf - α的转录和翻译。相反，通过这一途径感染促进了抗炎细胞因子IL-6和IL-10的表达和合成。此外，本研究表明，AIDE感染途径还通过破坏NOS基因转录因子IRF-1的转录和阻断STAT-1的激活来抑制先天抗denv介质一氧化氮自由基。总之，AIDE感染不仅促进了进入过程，还改变了先天和适应性的细胞内抗病毒机制，导致THP-1细胞中DENV的无限制复制。
The immunopathogenesis of dengue haemorrhagic fever and dengue shock syndrome is thought to be mediated by a variety of host factors. Enhancing antibodies are one of the key regulating molecules. These antibodies, via anti body-dependent enhancement (ADE) of infection, are able to facilitate dengue virus (DENV) growth in Fc-bearing host cells. The mechanism of ADE-enhanced DENV production is believed to be mediated through increasing the infected-cell mass. In the present work, the effect of AIDE infection was explored further, focusing on the post-entry events of AIDE infection. It was hypothesized that the higher virus production in AIDE infection compared with DENV infection may be due to the ability of this infection pathway to suppress key antiviral molecules. Therefore, the influence of AIDE infection on pro- and anti-inflammatory cytokines, including interleukin-1 2 (IL-12), gamma interferon (IFN-gamma), tumour necrosis factor alpha (TNF-alpha), IL-6 and IL-10, was investigated and it was found that DENV infection via the Fc receptor-mediated pathway was able to suppress the transcription and translation of L-12, IFN-gamma and TNIF-alpha. In contrast, infection via this route facilitated expression and synthesis of the anti-inflammatory cytokines IL-6 and IL-10. Moreover, this study demonstrates that the AIDE infection pathway also suppresses an innate anti-DENV mediator, nitric oxide radicals, by disrupting the transcription of the NOS gene transcription factor, IRF-1, and blocking the activation of STAT-1. In conclusion, AIDE infection not only facilitates the entry process, but also modifies innate and adaptive intracellular antiviral mechanisms, resulting in unrestricted DENV replication in THP-1 cells.