Dengue virus infection promotes translocation of high mobility group box 1 protein from the nucleus to the cytosol in dendritic cells, upregulates cytokine production and modulates virus replication

Dengue virus infection promotes translocation of high mobility group box 1 protein from the nucleus to the cytosol in dendritic cells, upregulates cytokine production and modulates virus replication
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DOI:
10.1099/vir.0.009027-0
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发表时间:
2009-08-01
影响因子:
3.8
通讯作者:
Palmer, Dupeh R.
Palmer, Dupeh R.
中科院分区:
医学3区
文献类型:
--
作者:
Kamau, Edwin;Takhampunya, Ratree;Palmer, Dupeh R.

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高迁移率族蛋白 1 (HMGB1) 蛋白在转录、细胞激活和促炎症反应的调节中发挥作用。然而,HMGB1 在病毒感染过程中的潜在作用尚未得到研究。本研究试图阐明 HMGB1 介导的炎症反应是否与登革热病毒 (DENV) 感染的发病机制有关。我们的数据显示,在非坏死条件下,人类树突状细胞 (DC) 以低 DENV 感染水平(复数为 1)释放 HMGB1。当感染 DENV 的 DC 与自体 T 细胞共培养时,两种细胞类型的 HMGB1 产量都会增加。 HMGB1 调节 DENV 感染的 DC 中肿瘤坏死因子 α、白细胞介素 (IL)-6、IL-8 和 α 干扰素的分泌。此外,HMGB1 产量的增加与 DC 中 DENV 复制滴度的降低有关。这些结果表明 HMGB1 的产生影响易感宿主中的 DENV 感染。
High mobility group box 1 (HMGB1) protein functions in regulation of transcription, cellular activation and pro-inflammatory responses. However, the potential role of HMGB1 during viral infection has not been investigated. This study attempted to elucidate whether the HMGB1-mediated inflammatory response contributes to the pathogenesis of dengue virus (DENV) infection. Our data showed that HMGB1 was released at low DENV infection levels (m.o.i. of 1) under non-necrotic conditions by human dendritic cells (DCs). When DENV-infected DCs were co-cultured with autologous T cells, there was increased production of HMGB1 by both cell types. HMGB1 regulated tumour necrosis factor alpha, interleukin (IL)-6, IL-8 and alpha interferon secretion in DENV-infected DCs. Additionally, increased HMGB1 production was associated with reduced DENV replication titres in DCs. These results suggest that HMGB1 production influences DENV infection in susceptible hosts.