Research Papers:

Proteomic analysis of chicken embryo fibroblast cells infected with recombinant H5N1 avian influenza viruses with and without NS1 eIF4GI binding domain

Kelei Guo, Xian Lin, Yongtao Li, Wei Qian, Zhong Zou, Huanchun Chen, Hongbo Zhou, _ Meilin Jin

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Oncotarget. 2018; 9:8350-8367. https://doi.org/10.18632/oncotarget.23615

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Kelei Guo1,2,3,4, Xian Lin1,2,3,4, Yongtao Li1,5, Wei Qian1,2,3,4, Zhong Zou1,2,3,4, Huanchun Chen1,2,3,4, Hongbo Zhou1,2,3,4 and Meilin Jin1,2,3,4

1State Key Laboratory of Agriculture Microbiology, Huazhong Agricultural University, Wuhan, 430070, P. R. China

2Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, P. R. China

3Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, 430070, P. R. China

4The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, P. R. China

5College of Animal Husbandry and Veterinary Science, Henan Agricultural University, Zhengzhou, 450002, P. R. China

Correspondence to:

Hongbo Zhou, email: hbzhou@mail.hzau.edu.cn

Meilin Jin, email: jml8328@126.com

Keywords: H5N1 avian influenza viruses; NS1 eIF4GI binding domain; proteomic analysis; chicken embryo fibroblast; differentially expressed proteins

Received: July 12, 2017     Accepted: October 28, 2017     Published: December 22, 2017


Non-structural 1 (NS1) protein is a key virulence factor that regulates replication of influenza virus. A recombinant H5N1 virus lacking the eIF4GI-binding domain of NS1 (rNS1-SD30) exhibits significantly lower pathogenicity than H5N1 virus with an intact eIF4GI-binding domain (rNS1-wt). To further investigate this phenomenon, we performed comparative proteomics analyses to profile host proteins in chicken embryo fibroblasts (CEFs) infected with rNS1-wt and rNS1-SD30 viruses. In total, 81 differentially expressed (DE) proteins were identified at 12, 24, and 36 h post-infection. These proteins are mainly involved in the cytoskeletal, apoptotic and stress responses, transcription regulation, transport and metabolic processes, mRNA processing and splicing, and cellular signal transduction. Overexpression of DE proteins revealed that ANXA7 suppresses propagation of rNS1-SD30, but not rNS1-wt viruses. Moreover, ALDH7A1, ANXA7, and DCTN2 strongly enhanced IFN-β promoter activity induced by chicken MDA5 (chMDA5), and in the case of ANXA7, also by the rNS1-SD30 viral strain. NS1-wt co-transfection suppressed the ANXA7-mediated increase in IFN-β promoter activity induced by chMDA5. These findings highlight the role of NS1 eIF4GI binding domain in H5N1 pathogenicity, and may contribute to the design of antiviral strategies to reduce the high morbidity and mortality associated with this pathogen.

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