Oncotarget

Research Papers:

The innate immunity of guinea pigs against highly pathogenic avian influenza virus infection

Kun Zhang, Wei Wei Xu, Zhaowei Zhang, Jing Liu, Jing Li, Lijuan Sun, Weiyang Sun, Peirong Jiao, Xiaoyu Sang, Zhiguang Ren, Zhijun Yu, Yuanguo Li, Na Feng, Tiecheng Wang, Hualei Wang, Songtao Yang, Yongkun Zhao, Xuemei Zhang, Peter R. Wilker, WenJun Liu, Ming Liao, Hualan Chen, Yuwei Gao _ and Xianzhu Xia

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Oncotarget. 2017; 8:30422-30437. https://doi.org/10.18632/oncotarget.16503

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Abstract

Kun Zhang1,2, Wei wei Xu1, Zhaowei Zhang1, Jing liu1, Jing Li3, Lijuan Sun4, Weiyang Sun1, Peirong Jiao5, Xiaoyu Sang1, Zhiguang Ren1, Zhijun Yu1, Yuanguo Li1, Na Feng1, Tiecheng Wang1, Hualei Wang1, Songtao Yang1, Yongkun Zhao1, Xuemei Zhang4, Peter R. Wilker6, WenJun Liu3, Ming Liao5, Hualan Chen7, Yuwei Gao1, Xianzhu Xia1

1Key Laboratory of Jilin Province for Zoonosis Prevention and Control, The Military Veterinary Institute, Academy of Military Medical Science of PLA, Changchun, 130122, PR China

2Philips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University, Richmond, Virginia, 23298, USA

3CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, PR China

4Department of Influenza Vaccine, Changchun Institute of Biological Product, Changchun, 130062, PR China

5College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, PR China

6Department of Microbiology, University of Wisconsin La Crosse, La Crosse, Wisconsin, 54601, USA

7State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, PR China

Correspondence to:

Yuwei Gao, email: gaoyuwei@gmail.com

Xianzhu Xia, email: xiaxzh@cae.cn

Keywords: innate immunity, guinea pig, highly pathogenic avian influenza virus, GBP-1, RIG-I

Received: August 26, 2016    Accepted: February 27, 2017    Published: March 23, 2017

ABSTRACT

H5N1 avian influenza viruses are a major pandemic concern. In contrast to the highly virulent phenotype of H5N1 in humans and many animal models, guinea pigs do not typically display signs of severe disease in response to H5N1 virus infection. Here, proteomic and transcriptional profiling were applied to identify host factors that account for the observed attenuation of A/Tiger/Harbin/01/2002 (H5N1) virulence in guinea pigs. RIG-I and numerous interferon stimulated genes were among host proteins with altered expression in guinea pig lungs during H5N1 infection. Overexpression of RIG-I or the RIG-I adaptor protein MAVS in guinea pig cell lines inhibited H5N1 replication. Endogenous GBP-1 expression was required for RIG-I mediated inhibition of viral replication upstream of the activity of MAVS. Furthermore, we show that guinea pig complement is involved in viral clearance, the regulation of inflammation, and cellular apoptosis during influenza virus infection of guinea pigs. This work uncovers features of the guinea pig innate immune response to influenza that may render guinea pigs resistant to highly pathogenic influenza viruses.


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