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Virus-host interactome and proteomic survey of PMBCs from COVID-19 patients reveal potential virulence factors influencing SARS-CoV-2 pathogenesis

Jingjiao Li, Mingquan Guo, Xiaoxu Tian, Chengrong Liu, Xin Wang, Xing Yang, Ping Wu, Zixuan Xiao, View ORCID ProfileYafei Qu, Yue Yin, Joyce Fu, Zhaoqin Zhu, Zhenshan Liu, Chao Peng, Tongyu Zhu, Qiming Liang
doi: https://doi.org/10.1101/2020.03.31.019216
Jingjiao Li
1Research Center of Translational Medicine, Shanghai Children’s Hospital; Shanghai Institute of Immunology, Department of Immunology and Microbiology, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China
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Mingquan Guo
2Shanghai Institute of Phage, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China
3Department of Laboratory Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China
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Xiaoxu Tian
4National Facility for Protein Science in Shanghai, Zhangjiang Lab, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210, China
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Chengrong Liu
1Research Center of Translational Medicine, Shanghai Children’s Hospital; Shanghai Institute of Immunology, Department of Immunology and Microbiology, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China
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Xin Wang
1Research Center of Translational Medicine, Shanghai Children’s Hospital; Shanghai Institute of Immunology, Department of Immunology and Microbiology, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China
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Xing Yang
1Research Center of Translational Medicine, Shanghai Children’s Hospital; Shanghai Institute of Immunology, Department of Immunology and Microbiology, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China
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Ping Wu
4National Facility for Protein Science in Shanghai, Zhangjiang Lab, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210, China
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Zixuan Xiao
5Faculty of Medicine & Dentistry, University of Alberta, Alberta, Canada
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Yafei Qu
1Research Center of Translational Medicine, Shanghai Children’s Hospital; Shanghai Institute of Immunology, Department of Immunology and Microbiology, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China
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  • ORCID record for Yafei Qu
Yue Yin
4National Facility for Protein Science in Shanghai, Zhangjiang Lab, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210, China
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Joyce Fu
6Department of Statistics, University of California, Riverside, California, USA
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Zhaoqin Zhu
3Department of Laboratory Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China
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Zhenshan Liu
1Research Center of Translational Medicine, Shanghai Children’s Hospital; Shanghai Institute of Immunology, Department of Immunology and Microbiology, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China
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  • For correspondence: liangqiming@shsmu.edu.cn tyzhu@shphc.org.cn pengchao@sari.ac.cn zhenshan6@shsmu.edu.cn
Chao Peng
4National Facility for Protein Science in Shanghai, Zhangjiang Lab, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210, China
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  • For correspondence: liangqiming@shsmu.edu.cn tyzhu@shphc.org.cn pengchao@sari.ac.cn zhenshan6@shsmu.edu.cn
Tongyu Zhu
2Shanghai Institute of Phage, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China
7Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
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  • For correspondence: liangqiming@shsmu.edu.cn tyzhu@shphc.org.cn pengchao@sari.ac.cn zhenshan6@shsmu.edu.cn
Qiming Liang
1Research Center of Translational Medicine, Shanghai Children’s Hospital; Shanghai Institute of Immunology, Department of Immunology and Microbiology, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China
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  • For correspondence: liangqiming@shsmu.edu.cn tyzhu@shphc.org.cn pengchao@sari.ac.cn zhenshan6@shsmu.edu.cn
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ABSTRACT

The ongoing coronavirus disease (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a global public health concern due to relatively easy person-to-person transmission and the current lack of effective antiviral therapy. However, the exact molecular mechanisms of SARS-CoV-2 pathogenesis remain largely unknown. We exploited an integrated proteomics approach to systematically investigate intra-viral and virus-host interactomes for the identification of unrealized SARS-CoV-2 host targets and participation of cellular proteins in the response to viral infection using peripheral blood mononuclear cells (PBMCs) isolated from COVID-19 patients. Using this approach, we elucidated 251 host proteins targeted by SARS-CoV-2 and more than 200 host proteins that are significantly perturbed in COVID-19 derived PBMCs. From the interactome, we further identified that non-structural protein nsp9 and nsp10 interact with NKRF, a NF-КB repressor, and may precipitate the strong IL-8/IL-6 mediated chemotaxis of neutrophils and overexuberant host inflammatory response observed in COVID-19 patients. Our integrative study not only presents a systematic examination of SARS-CoV-2-induced perturbation of host targets and cellular networks to reflect disease etiology, but also reveals insights into the mechanisms by which SARS-CoV-2 triggers cytokine storms and represents a powerful resource in the quest for therapeutic intervention.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 02, 2020.
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Virus-host interactome and proteomic survey of PMBCs from COVID-19 patients reveal potential virulence factors influencing SARS-CoV-2 pathogenesis
Jingjiao Li, Mingquan Guo, Xiaoxu Tian, Chengrong Liu, Xin Wang, Xing Yang, Ping Wu, Zixuan Xiao, Yafei Qu, Yue Yin, Joyce Fu, Zhaoqin Zhu, Zhenshan Liu, Chao Peng, Tongyu Zhu, Qiming Liang
bioRxiv 2020.03.31.019216; doi: https://doi.org/10.1101/2020.03.31.019216
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Virus-host interactome and proteomic survey of PMBCs from COVID-19 patients reveal potential virulence factors influencing SARS-CoV-2 pathogenesis
Jingjiao Li, Mingquan Guo, Xiaoxu Tian, Chengrong Liu, Xin Wang, Xing Yang, Ping Wu, Zixuan Xiao, Yafei Qu, Yue Yin, Joyce Fu, Zhaoqin Zhu, Zhenshan Liu, Chao Peng, Tongyu Zhu, Qiming Liang
bioRxiv 2020.03.31.019216; doi: https://doi.org/10.1101/2020.03.31.019216

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