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
收藏
页码：1369 / 1380
页数：12
相关论文
共 42 条
[1]   Pathogenesis of influenza virus-induced pneumonia: Involvement of both nitric oxide and oxygen radicals [J].
Akaike, T ;
Noguchi, Y ;
Ijiri, S ;
Setoguchi, K ;
Suga, M ;
Zheng, YM ;
Dietzschold, B ;
Maeda, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (06) :2448-2453
[2]   Nitric oxide and virus infection [J].
Akaike, T ;
Maeda, H .
IMMUNOLOGY, 2000, 101 (03) :300-308
[3]   ATM-ROS-iNOS axis regulates nitric oxide mediated cellular senescence [J].
Bagheri, Meisam ;
Nair, Raji R. ;
Singh, Krishna Kumar ;
Saini, Deepak Kumar .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2017, 1864 (01) :177-190
[4]   Transmission of H7N9 influenza virus in mice by different infective routes [J].
Bao, Linlin ;
Xu, Lili ;
Zhu, Hua ;
Deng, Wei ;
Chen, Ting ;
Lv, Qi ;
Li, Fengdi ;
Yuan, Jing ;
Xu, Yanfeng ;
Huang, Lan ;
Li, Yanhong ;
Liu, Jiangning ;
Yao, Yanfeng ;
Yu, Pin ;
Chen, Honglin ;
Qin, Chuan .
VIROLOGY JOURNAL, 2014, 11
[5]   Pathogenesis of avian influenza (H7) virus infection in mice and ferrets: Enhanced virulence of Eurasian H7N7 viruses isolated from humans [J].
Belser, Jessica A. ;
Lu, Xuihua ;
Maines, Taronna R. ;
Smith, Catherine ;
Li, Yan ;
Donis, Ruben O. ;
Katz, Jacqueline M. ;
Tumpey, Terrence M. .
JOURNAL OF VIROLOGY, 2007, 81 (20) :11139-11147
[6]   Inhibition of p38 Mitogen-activated Protein Kinase Impairs Influenza Virus-induced Primary and Secondary Host Gene Responses and Protects Mice from Lethal H5N1 Infection [J].
Boergeling, Yvonne ;
Schmolke, Mirco ;
Viemann, Dorothee ;
Nordhoff, Carolin ;
Roth, Johannes ;
Ludwig, Stephan .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2014, 289 (01) :13-27
[7]   APOPTOSIS AND NECROSIS - 2 DISTINCT EVENTS INDUCED, RESPECTIVELY, BY MILD AND INTENSE INSULTS WITH N-METHYL-D-ASPARTATE OR NITRIC-OXIDE SUPEROXIDE IN CORTICAL CELL-CULTURES [J].
BONFOCO, E ;
KRAINC, D ;
ANKARCRONA, M ;
NICOTERA, P ;
LIPTON, SA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (16) :7162-7166
[8]   Cellular longevity: role of apoptosis and replicative senescence [J].
Bree, RT ;
Stenson-Cox, C ;
Grealy, M ;
Byrnes, L ;
Gorman, AM ;
Samali, A .
BIOGERONTOLOGY, 2002, 3 (04) :195-206
[9]   Tumor necrosis factor-α and phorbol 12-myristate 13-acetate differentially modulate cytotoxic effect of nitric oxide generated by serum deprivation in neuronal PC12 cells [J].
Chung, KC ;
Park, JH ;
Kim, CH ;
Ahn, YS .
JOURNAL OF NEUROCHEMISTRY, 1999, 72 (04) :1482-1488
[10]   Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor [J].
Coppe, Jean-Philippe ;
Patil, Christopher K. ;
Rodier, Francis ;
Sun, Yu ;
Munoz, Denise P. ;
Goldstein, Joshua ;
Nelson, Peter S. ;
Desprez, Pierre-Yves ;
Campisi, Judith .
PLOS BIOLOGY, 2008, 6 (12) :2853-2868
12345