title: iTRAQ-based quantitative proteomics reveals important host factors involved in the high pathogenicity of the H5N1 avian influenza virus in mice.
abstract: We previously reported a pair of H5N1 avian influenza viruses which are genetically similar but differ greatly in their virulence in mice. A/Chicken/Jiangsu/k0402/2010 (CK10) is highly lethal to mice, whereas A/Goose/Jiangsu/k0403/2010 (GS10) is avirulent. In this study, to investigate the host factors that account for their virulence discrepancy, we compared the pathology and host proteome of the CK10- or GS10-infected mouse lung. Moderate lung injury was observed from CK10-infected animals as early as the first day of infection, and the pathology steadily progressed at later time point. However, only mild lesions were observed in GS10-infected mouse lung at the late infection stage. Using the quantitative iTRAQ coupled LC-MS/MS method, we first found that more significantly differentially expressed (DE) proteins were stimulated by GS10 compared with CK10. However, bio-function analysis of the DE proteins suggested that CK10 induced much stronger inflammatory response-related functions than GS10. Canonical pathway analysis also demonstrated that CK10 highly activated the "Acute Phase Response Signaling," which results in a wide range of biological activities in response to viral infection, including many inflammatory processes. Further in-depth analysis showed that CK10 exacerbated acute lung injury-associated responses, including inflammatory response, cell death, reactive oxygen species production and complement response. In addition, some of these identified proteins that associated with the lung injury were further confirmed to be regulated in vitro. Therefore, our findings suggest that the early increased lung injury-associated host response induced by CK10 may contribute to the lung pathology and the high virulence of this virus in mice.
authors.affiliation: Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, 48 East Wenhui Road, Yangzhou, 225009, Jiangsu Province, China.|Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, 225009, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Hu
authors.affiliation: Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, 48 East Wenhui Road, Yangzhou, 225009, Jiangsu Province, China.|Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, 225009, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, 48 East Wenhui Road, Yangzhou, 225009, Jiangsu Province, China.|Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, 225009, China.
authors.forename: Xiaoquan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, 48 East Wenhui Road, Yangzhou, 225009, Jiangsu Province, China.|Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, 225009, China.
authors.forename: Min
authors.initials: M
authors.lastname: Gu
authors.affiliation: Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, 48 East Wenhui Road, Yangzhou, 225009, Jiangsu Province, China.|Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, 225009, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, 48 East Wenhui Road, Yangzhou, 225009, Jiangsu Province, China.|Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, 225009, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liu
authors.affiliation: Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, 48 East Wenhui Road, Yangzhou, 225009, Jiangsu Province, China.|Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, 225009, China.
authors.forename: Shunlin
authors.initials: S
authors.lastname: Hu
authors.affiliation: Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, 48 East Wenhui Road, Yangzhou, 225009, Jiangsu Province, China.|Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, 225009, China.
authors.forename: Huimou
authors.initials: H
authors.lastname: Liu
authors.affiliation: Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, 48 East Wenhui Road, Yangzhou, 225009, Jiangsu Province, China.|Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, 225009, China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Liu
authors.affiliation: Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, 48 East Wenhui Road, Yangzhou, 225009, Jiangsu Province, China.|Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, 225009, China.
authors.forename: Sujuan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, 48 East Wenhui Road, Yangzhou, 225009, Jiangsu Province, China.|Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, 225009, China.
authors.forename: Daxin
authors.initials: D
authors.lastname: Peng
authors.affiliation: Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, 48 East Wenhui Road, Yangzhou, 225009, Jiangsu Province, China. xfliu@yzu.edu.cn.|Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, 225009, China. xfliu@yzu.edu.cn.
authors.forename: Xiufan
authors.initials: X
authors.lastname: Liu
mesh_terms: D000210:Acute-Phase Reaction / Q000378:metabolism / Q000821:virology; D000818:Animals; D002450:Cell Communication; D002460:Cell Line; D002853:Chromatography, Liquid; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D005260:Female; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000472:pathogenicity; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000821:virology*; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D020543:Proteome; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry
chemical_list: D020543:Proteome
keywords: Highly pathogenic H5N1 virus; Lung injury; Pathogenesis; Proteomics; iTRAQ