Oncotarget

Research Papers:

Autophagy is highly targeted among host comparative proteomes during infection with different virulent RABV strains

Ling Li, Hongli Jin, Hualei Wang _, Zengguo Cao, Na Feng, Jianzhong Wang, Yongkun Zhao, Xuexing Zheng, Pengfei Hou, Nan Li, Hang Chi, Pei Huang, Cuicui Jiao, Qian Li, Lina Wang, Tiecheng Wang, Weiyang Sun, Yuwei Gao, Changchun Tu, Guixue Hu, Songtao Yang and Xianzhu Xia

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Oncotarget. 2017; 8:21336-21350. https://doi.org/10.18632/oncotarget.15184

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Abstract

Ling Li1,2, Hongli Jin1,2, Hualei Wang2,4, Zengguo Cao2, Na Feng2,4, Jianzhong Wang3, Yongkun Zhao2, Xuexing Zheng2,5, Pengfei Hou1,2, Nan Li2, Hang Chi2, Pei Huang2,3, Cuicui Jiao2, Qian Li2, Lina Wang2,3, Tiecheng Wang2, Weiyang Sun2, Yuwei Gao2,4, Changchun Tu2, Guixue Hu3, Songtao Yang2,4, Xianzhu Xia2,4

1Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, China

2Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China

3Department of Preventive Veterinary Medicine, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China

4Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou, China

5School of Public Health, Shandong University, Jinan, China

Correspondence to:

Hualei Wang email: [email protected]

Songtao Yang email: [email protected]

Guixue Hu email: [email protected]

Keywords: rabies virus, proteome, proteomics analysis, autophagy, differential virulence

Received: May 23, 2016    Accepted: January 16, 2017    Published: February 08, 2017

ABSTRACT

Rabies virus (RABV) is a neurotropic virus that causes serious disease in humans and animals worldwide. It has been reported that different RABV strains can result in divergent prognoses in animal model. To identify host factors that affect different infection processes, a kinetic analysis of host proteome alterations in mouse brains infected with different virulent RABV strains was performed using isobaric tags for a relative and absolute quantification (iTRAQ)-liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics approach, and this analysis identified 147 differentially expressed proteins (DEPs) between the pathogenic challenge virus standard (CVS)-11 strain and the attenuated SRV9 strain. Bioinformatics analyses of these DEPs revealed that autophagy and several pathways associated with autophagy, such as mammalian target of rapamycin (mTOR) signaling, p70S6K signaling, nuclear factor erythroid 2-related factor 2 (NRF2)-mediated oxidative stress and superoxide radical degradation, were dysregulated. Validation of the proteomic data showed that attenuated SRV9 induced more autophagosome accumulation than CVS-11 in an in vitro model. Our findings provide new insights into the pathogenesis of RABV and encourage further studies on this topic.


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