Dengue virus infection induces formation of G3BP1 granules in human lung epithelial cells
Dengue virus infection induces formation of G3BP1 granules in human lung epithelial cells
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DOI：
10.1007/s00705-015-2578-9
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发表时间：
2015-09
影响因子：
2.7
通讯作者：
Jun Xia;Xiaoyan Chen;Feng Xu;Yi Wang;Yong-hua Shi;Yu-ye Li;Junfang He;Ping Zhang
中科院分区：
文献类型：
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作者：
Jun Xia;Xiaoyan Chen;Feng Xu;Yi Wang;Yong-hua Shi;Yu-ye Li;Junfang He;Ping Zhang
细胞对病毒感染进行重编程，导致应激颗粒（SG）的形成，而病毒已经进化出多种策略来拮抗宿主SG反应。以往的文献报道，在BHK-1细胞中，感染登革病毒（DENV）干扰SG的形成。在本研究中，我们通过检测两个SG标志物TIA-1和G3 BP 1的亚细胞定位进一步研究了人上皮A549细胞中SG的形成。为了响应DENV 2型（DENV 2）和3型（DENV 3）感染，G3 BP 1（而不是TIA-1）被招募到一些细胞的细胞质颗粒中，并且含有G3 BP 1颗粒的细胞中的病毒蛋白质合成显着受损。G3 BP 1的敲低显著地挽救了dsRNA介导的对DENV 2复制的抑制。此外，我们的数据表明，由dsRNA（PKR）和eIF 2 α调节的蛋白激酶磷酸化以及dsRNA的积累主要发生在病毒感染的后期。这项工作表明，在DENV感染的A549细胞中，G3 BP 1颗粒独立于TIA-1组装，并对病毒复制产生负面影响。这扩展了我们对SG反应和登革病毒感染之间的拮抗关系的理解。
Cells reprogram ongoing translation in response to viral infection, resulting in formation of stress granules (SGs), while viruses have evolved a variety of strategies to antagonize the host SG response. Previous literature reported that in BHK-1 cells, infection with dengue virus (DENV) interfered with the SG formation. In the current study, we further investigated SG formation in human epithelial A549 cells by detecting subcellular localization of two SG hallmarks, TIA-1 and G3BP1. In response to DENV type 2 (DENV2) and type 3 (DENV3) infection, G3BP1, but not TIA-1, was recruited into cytoplasmic granules in some cells, and viral protein synthesis was significantly impaired in the G3BP1-granule-containing cells. Knockdown of G3BP1 significantly rescued the dsRNA-mediated suppression of DENV2 replication. Furthermore, our data showed that the phosphorylation of protein kinase regulated by dsRNA (PKR) and eIF2α, as well as accumulation of dsRNA, mainly occurred at the late stage of viral infection. This work revealed that in DENV-infected A549 cells, G3BP1 granules were assembled independently of TIA-1 and had a negative impact on viral replication. This extends our understanding of the antagonistic relationship between the SG response and dengue virus infection.