Porcine Reproductive and Respiratory Syndrome Virus Infection Induces Stress Granule Formation Depending on Protein Kinase R-like Endoplasmic Reticulum Kinase (PERK) in MARC-145 Cells.
Porcine Reproductive and Respiratory Syndrome Virus Infection Induces Stress Granule Formation Depending on Protein Kinase R-like Endoplasmic Reticulum Kinase (PERK) in MARC-145 Cells.
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猪繁殖与呼吸综合征病毒感染诱导 MARC-145 细胞中依赖于蛋白激酶 R 样内质网激酶 (PERK) 的应激颗粒形成
DOI：
10.3389/fcimb.2017.00111
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发表时间：
2017
影响因子：
5.7
通讯作者：
Xiao S
中科院分区：
文献类型：
--
作者：
Zhou Y;Fang L;Wang D;Cai K;Chen H;Xiao S
应激颗粒(SGS)是在包括病毒感染在内的各种应激条件下形成的mRNA储存场所。猪繁殖与呼吸综合征病毒(PRRSV)是一种动脉病毒，自20世纪80年代末以来一直在全球养猪业造成严重破坏。在本研究中，我们发现PRRSV WUH3株(基因2型PRRSV)感染后，在MARC-145细胞中稳定地形成了健壮的SGS，SGS的标志性蛋白包括TIA1、G3BP1和eIF3η的募集证明了这一点。用特定的抑制剂或siRNAs处理参与SG形成的应激蛋白激酶，发现PRRSV通过一种依赖于PERK(蛋白激酶R样内质网状激酶)的机制诱导SG的形成。同时敲除SG标志蛋白(TIA1、G3BP1和TIAR)对SG组装的损害不影响PRRSV的生长，但显著增强PRRSV诱导的NF-κB亚单位p65的磷酸化和炎性细胞因子的产生。综上所述，我们的结果表明，PRRSV通过PERK依赖的途径诱导SG的形成，SGS参与了PRRSV诱导的Marc-145细胞炎症反应的信号通路。
Stress granules (SGs) are sites of mRNA storage that are formed in response to various conditions of stress, including viral infections. Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has been devastating the swine industry worldwide since the late 1980s. In this study, we found that infection of PRRSV strain WUH3 (genotype 2 PRRSV) induced stable formation of robust SGs in MARC-145 cells, as demonstrated by the recruitment of marker proteins of SGs, including TIA1, G3BP1, and eIF3η. Treatment with specific inhibitors or siRNAs against the stress kinases that are involved in SG formation revealed that PRRSV induced SG formation through a PERK (protein kinase R–like endoplasmic reticulum kinase)-dependent mechanism. Impairment of SG assembly by concomitant knockdown of the SG marker proteins (TIA1, G3BP1, and TIAR) did not affect PRRSV growth, while significantly enhanced PRRSV-induced NF-κB subunit p65 phosphorylation and inflammatory cytokine production. Taken together, our results demonstrate that PRRSV induces SG formation via a PERK-dependent pathway and that SGs are involved in the signaling pathway of the PRRSV-induced inflammatory response in MARC-145 cells.