Distinct regulation of host responses by ERK and JNK MAP kinases in swine macrophages infected with pandemic (H1N1) 2009 influenza virus.
Distinct regulation of host responses by ERK and JNK MAP kinases in swine macrophages infected with pandemic (H1N1) 2009 influenza virus.
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感染 2009 年 H1N1 流感病毒的猪巨噬细胞中 ERK 和 JNK MAP 激酶对宿主反应的独特调节
DOI：
10.1371/journal.pone.0030328
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Xing Z
中科院分区：
文献类型：
--
作者：
Gao W;Sun W;Qu B;Cardona CJ;Powell K;Wegner M;Shi Y;Xing Z
猪流感是由猪流感病毒（SIV）引起的猪的急性呼吸道疾病。高毒力的SIV毒株导致高达10%的死亡率。重要的是，猪长期以来一直被认为是产生具有大流行潜力的新型流感病毒的“混合容器”，对公共卫生构成持续威胁。自2009年出现和随后的大流行传播以来，2009年大流行（H1N1）（H1N1 pdm）已在养猪场中被发现，产生了产生新的免疫原的风险，并可能感染人类。SIV或H1N1 pdm感染猪的发病机制仍不清楚。促炎和抗病毒细胞因子反应被认为与临床体征的强度相关，并且发现猪巨噬细胞在从猪肺有效清除SIV中是不可或缺的。在这项研究中，我们报告了一个独特的模式，细胞因子的反应在猪巨噬细胞感染H1N1 pdm。丝裂原活化蛋白（MAP）激酶在调节宿主反应中的作用进行了研究。我们发现促炎细胞因子IL-6、IL-8、IL-10和TNF-α被显著诱导，并且它们的诱导是ERK 1/2依赖性的。IFN-β和IFN诱导的抗病毒药物Mx和2′5′-OAS可被强烈诱导，但当ERK 1/2被抑制时，诱导作用被有效地消除。CCL 5（RANTES）的诱导被ERK 1/2和JNK 1/2的抑制剂完全抑制，这似乎也调节FasL和TNF-α，这对猪巨噬细胞的凋亡至关重要。我们发现NFκB在H1N1 pdm感染的细胞中被激活，但是当ERK 1/2被抑制时，NF κ B的激活被抑制，这表明在猪巨噬细胞中MAP激酶和NFκB反应之间存在交叉作用。我们的数据表明，MAP激酶可能通过诱导RIG-1激活NFκB，从而诱导猪巨噬细胞产生IFN-β。了解宿主反应及其潜在机制可能有助于确定有效控制SIV的场所，并有助于预防未来的流感大流行。
Swine influenza is an acute respiratory disease in pigs caused by swine influenza virus (SIV). Highly virulent SIV strains cause mortality of up to 10%. Importantly, pigs have long been considered “mixing vessels” that generate novel influenza viruses with pandemic potential, a constant threat to public health. Since its emergence in 2009 and subsequent pandemic spread, the pandemic (H1N1) 2009 (H1N1pdm) has been detected in pig farms, creating the risk of generating new reassortants and their possible infection of humans. Pathogenesis in SIV or H1N1pdm-infected pigs remains poorly characterized. Proinflammatory and antiviral cytokine responses are considered correlated with the intensity of clinical signs, and swine macrophages are found to be indispensible in effective clearance of SIV from pig lungs. In this study, we report a unique pattern of cytokine responses in swine macrophages infected with H1N1pdm. The roles of mitogen-activated protein (MAP) kinases in the regulation of the host responses were examined. We found that proinflammatory cytokines IL-6, IL-8, IL-10, and TNF-α were significantly induced and their induction was ERK1/2-dependent. IFN-β and IFN-inducible antiviral Mx and 2′5′-OAS were sharply induced, but the inductions were effectively abolished when ERK1/2 was inhibited. Induction of CCL5 (RANTES) was completely inhibited by inhibitors of ERK1/2 and JNK1/2, which appeared also to regulate FasL and TNF-α, critical for apoptosis in pig macrophages. We found that NFκB was activated in H1N1pdm-infected cells, but the activation was suppressed when ERK1/2 was inhibited, indicating there is cross-talk between MAP kinase and NFκB responses in pig macrophages. Our data suggest that MAP kinase may activate NFκB through the induction of RIG-1, which leads to the induction of IFN-β in swine macrophages. Understanding host responses and their underlying mechanisms may help identify venues for effective control of SIV and assist in prevention of future influenza pandemics.
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影响因子：
3.3
作者：
Vincent, Amy L.;Swenson, Sabrina L.;Zhang, Yan
通讯作者：
Zhang, Yan
影响因子：
5.5
作者：
Van Reeth, K;Gregory, V;Pensaert, M
通讯作者：
Pensaert, M
影响因子：
56.9
作者：
Pichlmair, Andreas;Schulz, Oliver;Sousa, Caetano Reis E.
通讯作者：
Sousa, Caetano Reis E.
DOI：
10.1128/aem.16.4.588-594.1968
发表时间：
1968-01-01
期刊：
APPLIED MICROBIOLOGY
影响因子：
--
作者：
GAUSH, CR;SMITH, TF
通讯作者：
SMITH, TF
DOI：
10.1196/annals.1373.014
发表时间：
2006-01-01
期刊：
IMPACT OF EMERGING ZOONOTIC DISEASES ON ANIMAL HEALTH
影响因子：
--
作者：
Charley, Bernard;Riffault, Sabine;Van Reeth, Kristien
通讯作者：
Van Reeth, Kristien