NS1 of H7N9 Influenza A Virus Induces NO-Mediated Cellular Senescence in Neuro2a Cells

被引：16

作者：

Yan, Yinxia ^{[1
]}

Du, Yongming ^{[2
]}

Zheng, Huali ^{[1
]}

Wang, Gefei ^{[1
]}

Li, Rui ^{[1
]}

Chen, Jieling ^{[3
]}

Li, Kangsheng ^{[1
]}

机构：

[1] Shantou Univ, Dept Microbiol & Immunol, Key Lab Infect Dis & Mol Immunopathol Guangdong P, Med Coll, Shantou, Guangdong, Peoples R China

[2] Univ Hong Kong, Dept Biochem, Hong Kong, Hong Kong, Peoples R China

[3] Shantou Univ, Shantou Oxford Clin Res Unit, Med Coll, Shantou, Guangdong, Peoples R China

来源：

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY | 2017年 / 43卷 / 04期

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

H7N9 influenza virus; NS1; Nitric oxide; Cellular senescence; p38; MAPK; ACTIVATED PROTEIN-KINASE; NITRIC-OXIDE SYNTHASE; CENTRAL-NERVOUS-SYSTEM; INDUCED-APOPTOSIS; INFECTION; MICE; EXPRESSION; H5N1; PATHOGENESIS; MANIFESTATIONS;

D O I：

10.1159/000481848

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Background/Aims: The novel avian H7N9 influenza A virus has been detected in brain tissues and associated with central nervous system (CNS) symptoms in infected human and mice. Roles of its virulence factor, NS1 protein in influenza virus infected neuron has yet to be explored. Methods: Nitric oxide (NO) release and inducible nitric oxide synthase (iNOS) expression in H7N9/NS1-expressed Neuro2a cells were detected by Griess test and western blotting. Cell proliferation rate of H7N9/NS1-expressing cells was recorded by Cell Counting Kit-8. Effects of H7N9/NS1 on cellular senescence were investigated by senescenceassociated beta-galactosidase (SA-beta-gal) staining, immunofluorescent staining of phosphorylated heterochromatin protein 1 gamma (pHP1 gamma) and qPCR analysis of IL-6 and IL-8. Results: H7N9/NS1 in Neuro2a cells and primary cultured mouse cortical neurons increased the expression of iNOS and boosted NO release. Neuro2a cells constitutively expressing NS1 displayed a reduced proliferative ability, enhanced SA-beta-gal staining, increased level of IL-6 and IL-8 and a typical punctuate structure of pHP1 gamma in nuclei. In addition, p38 MAPK was elevated in NS1-expressing Neuro2a cells. Reduced iNOS expression and subdued cellular senescence effect was found in p38 MAPK inhibitor-treated NS1-expressing Neuro2a cells. Conclusion: Our results suggest that H7N9/NS1 protein increases the iNOS expression and NO release in Neuro2a cells, which can induce cell growth arrest and cellular senescence. (C) 2017 The Author(s) Published by S. Karger AG, Basel

引用

页码：1369 / 1380

页数：12

共 42 条

[41] The Novel H7N9 Influenza A Virus NS1 Induces p53-Mediated Apoptosis of A549 Cells [J].