Apoptotic and Early Innate Immune Responses to PB1-F2 Protein of Influenza A Viruses Belonging to Different Subtypes in Human Lung Epithelial A549 Cells.

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Accounts of Chemical Research Pub Date : 2018-12-31 eCollection Date: 2018-01-01 DOI:10.1155/2018/5057184
Gunisha Pasricha, Sanjay Mukherjee, Alok K Chakrabarti
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引用次数: 7

Abstract

PB1-F2 is a multifunctional protein and contributes to the pathogenicity of influenza A viruses. PB1-F2 is known to have strain and cell specific functions. In this study we have investigated the apoptotic and inflammatory responses of PB1-F2 protein from influenza viruses of diverse pathogenicities in A549 lung epithelial cells. Overexpression of PB1-F2 resulted in apoptosis and heightened inflammatory response in A549 cells. Comparison revealed that the response varied with each subtype. PB1-F2 protein from highly pathogenic H5N1 virus induced least apoptosis but maximum inflammatory response. Results indicated that apoptosis was mediated through death receptor ligands TNFα and TRAIL via Caspase 8 activation. Significant induction of cytokines/chemokines CXCL10, CCL5, CCL2, IFNα, and IL-6 was noted in A549 cells transfected with PB1-F2 gene construct of 2008 West Bengal H5N1 virus (H5N1-WB). On the contrary, PB1-F2 construct from 2007 highly pathogenic H5N1 isolate (H5N1-M) with truncated N-terminal region did not evoke as exuberant inflammatory response as the other H5N1-WB with full length PB1-F2, signifying the importance of N-terminal region of PB1-F2. Sequence analysis revealed that PB1-F2 proteins derived from different influenza viruses varied at multiple amino acid positions. The secondary structure prediction showed each of the PB1-F2 proteins had distinct helix-loop-helix structure. Thus, our data substantiate the notion that the contribution of PB1-F2 to influenza pathogenicity is greatly strain specific and involves multiple host factors. This data demonstrates that PB1-F2 protein of influenza A virus, when expressed independently is minimally apoptotic and strongly influences the early host response in A549 cells.

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人肺上皮A549细胞不同亚型甲型流感病毒对PB1-F2蛋白的凋亡和早期先天免疫应答
PB1-F2是一种多功能蛋白,参与甲型流感病毒的致病性。已知PB1-F2具有菌株和细胞特异性功能。在这项研究中,我们研究了不同致病性流感病毒对A549肺上皮细胞中PB1-F2蛋白的凋亡和炎症反应。过表达PB1-F2导致A549细胞凋亡和炎症反应增强。比较显示,每个亚型的反应不同。来自高致病性H5N1病毒的PB1-F2蛋白诱导的细胞凋亡最少,但炎症反应最大。结果表明,凋亡是通过死亡受体配体TNFα和TRAIL激活Caspase 8介导的。转染2008年西孟加拉邦H5N1病毒(H5N1- wb) PB1-F2基因构建体的A549细胞显著诱导细胞因子/趋化因子CXCL10、CCL5、CCL2、IFNα和IL-6。与此相反,2007年高致病性H5N1分离株(H5N1- m)中n端被截断的PB1-F2构建体没有像其他全长PB1-F2的H5N1- wb那样引起旺盛的炎症反应,这表明PB1-F2 n端区域的重要性。序列分析显示,来自不同流感病毒的PB1-F2蛋白在多个氨基酸位置上存在差异。二级结构预测表明,PB1-F2蛋白具有不同的螺旋-环-螺旋结构。因此,我们的数据证实了PB1-F2对流感致病性的贡献在很大程度上是菌株特异性的,涉及多种宿主因素。这些数据表明,甲型流感病毒的PB1-F2蛋白在A549细胞中独立表达时凋亡最小,并强烈影响宿主的早期反应。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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