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Virus-Host Interactome and Proteomic Survey Reveal Potential Virulence Factors Influencing SARS-CoV-2 Pathogenesis.
Med (N Y). 2021 Jan 15; 2(1):99-112.e7.M

Abstract

Background

The ongoing coronavirus disease 2019 (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.

Methods

Genome-wide screening was used to establish intraviral and viral-host interactomes. Quantitative proteomics was used to investigate the peripheral blood mononuclear cell (PBMC) proteome signature in COVID-19.

Findings

We elucidated 286 host proteins targeted by SARS-CoV-2 and >350 host proteins that are significantly perturbed in COVID-19-derived PBMCs. This signature in severe COVID-19 PBMCs reveals a significant upregulation of cellular proteins related to neutrophil activation and blood coagulation, as well as a downregulation of proteins mediating T cell receptor signaling. From the interactome, we further identified that non-structural protein 10 interacts with NF-κB-repressing factor (NKRF) to facilitate interleukin-8 (IL-8) induction, which potentially contributes to IL-8-mediated chemotaxis of neutrophils and the overexuberant host inflammatory response observed in COVID-19 patients.

Conclusions

Our study not only presents a systematic examination of SARS-CoV-2-induced perturbation of host targets and cellular networks but it also reveals insights into the mechanisms by which SARS-CoV-2 triggers cytokine storms, representing a powerful resource in the pursuit of therapeutic interventions.

Funding

National Key Research and Development Project of China, National Natural Science Foundation of China, National Science and Technology Major Project, Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning, Shanghai Science and Technology Commission, Shanghai Municipal Health Commission, Shanghai Municipal Key Clinical Specialty, Innovative Research Team of High-level Local Universities in Shanghai, Interdisciplinary Program of Shanghai Jiao Tong University, SII Challenge Fund for COVID-19 Research, Chinese Academy of Sciences (CAS) Large Research Infrastructure of Maintenance and Remolding Project, and Chinese Academy of Sciences Key Technology Talent Program.

Authors+Show Affiliations

Research Center of Translational Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China. Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.Shanghai Institute of Phage, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China. Department of Laboratory Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.National Facility for Protein Science in Shanghai, Zhangjiang Lab, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China.Research Center of Translational Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China. Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.Research Center of Translational Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China. Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.National Facility for Protein Science in Shanghai, Zhangjiang Lab, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China.Research Center of Translational Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China. Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.Department of Medicine, University of Alberta, Edmonton, AB, Canada.Research Center of Translational Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China. Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.National Facility for Protein Science in Shanghai, Zhangjiang Lab, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China.Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200062, China.Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200062, China.Department of Laboratory Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.Research Center of Translational Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China. Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.National Facility for Protein Science in Shanghai, Zhangjiang Lab, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China.Shanghai Institute of Phage, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China. Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Fudan University, Shanghai 200032, China.Research Center of Translational Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China. Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32838362

Citation

Li, Jingjiao, et al. "Virus-Host Interactome and Proteomic Survey Reveal Potential Virulence Factors Influencing SARS-CoV-2 Pathogenesis." Med (New York, N.Y.), vol. 2, no. 1, 2021, pp. 99-112.e7.
Li J, Guo M, Tian X, et al. Virus-Host Interactome and Proteomic Survey Reveal Potential Virulence Factors Influencing SARS-CoV-2 Pathogenesis. Med (N Y). 2021;2(1):99-112.e7.
Li, J., Guo, M., Tian, X., Wang, X., Yang, X., Wu, P., Liu, C., Xiao, Z., Qu, Y., Yin, Y., Wang, C., Zhang, Y., Zhu, Z., Liu, Z., Peng, C., Zhu, T., & Liang, Q. (2021). Virus-Host Interactome and Proteomic Survey Reveal Potential Virulence Factors Influencing SARS-CoV-2 Pathogenesis. Med (New York, N.Y.), 2(1), 99-e7. https://doi.org/10.1016/j.medj.2020.07.002
Li J, et al. Virus-Host Interactome and Proteomic Survey Reveal Potential Virulence Factors Influencing SARS-CoV-2 Pathogenesis. Med (N Y). 2021 Jan 15;2(1):99-112.e7. PubMed PMID: 32838362.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Virus-Host Interactome and Proteomic Survey Reveal Potential Virulence Factors Influencing SARS-CoV-2 Pathogenesis. AU - Li,Jingjiao, AU - Guo,Mingquan, AU - Tian,Xiaoxu, AU - Wang,Xin, AU - Yang,Xing, AU - Wu,Ping, AU - Liu,Chengrong, AU - Xiao,Zixuan, AU - Qu,Yafei, AU - Yin,Yue, AU - Wang,Chunxia, AU - Zhang,Yucai, AU - Zhu,Zhaoqin, AU - Liu,Zhenshan, AU - Peng,Chao, AU - Zhu,Tongyu, AU - Liang,Qiming, Y1 - 2020/07/21/ PY - 2020/05/28/received PY - 2020/06/27/revised PY - 2020/07/15/accepted PY - 2020/8/25/pubmed PY - 2020/8/25/medline PY - 2020/8/25/entrez KW - COVID-19 KW - IL-8 KW - NKRF KW - SARS-CoV-2 KW - interactome KW - nsp10 KW - proteomics SP - 99 EP - 112.e7 JF - Med (New York, N.Y.) JO - Med (N Y) VL - 2 IS - 1 N2 - Background: The ongoing coronavirus disease 2019 (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. Methods: Genome-wide screening was used to establish intraviral and viral-host interactomes. Quantitative proteomics was used to investigate the peripheral blood mononuclear cell (PBMC) proteome signature in COVID-19. Findings: We elucidated 286 host proteins targeted by SARS-CoV-2 and >350 host proteins that are significantly perturbed in COVID-19-derived PBMCs. This signature in severe COVID-19 PBMCs reveals a significant upregulation of cellular proteins related to neutrophil activation and blood coagulation, as well as a downregulation of proteins mediating T cell receptor signaling. From the interactome, we further identified that non-structural protein 10 interacts with NF-κB-repressing factor (NKRF) to facilitate interleukin-8 (IL-8) induction, which potentially contributes to IL-8-mediated chemotaxis of neutrophils and the overexuberant host inflammatory response observed in COVID-19 patients. Conclusions: Our study not only presents a systematic examination of SARS-CoV-2-induced perturbation of host targets and cellular networks but it also reveals insights into the mechanisms by which SARS-CoV-2 triggers cytokine storms, representing a powerful resource in the pursuit of therapeutic interventions. Funding: National Key Research and Development Project of China, National Natural Science Foundation of China, National Science and Technology Major Project, Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning, Shanghai Science and Technology Commission, Shanghai Municipal Health Commission, Shanghai Municipal Key Clinical Specialty, Innovative Research Team of High-level Local Universities in Shanghai, Interdisciplinary Program of Shanghai Jiao Tong University, SII Challenge Fund for COVID-19 Research, Chinese Academy of Sciences (CAS) Large Research Infrastructure of Maintenance and Remolding Project, and Chinese Academy of Sciences Key Technology Talent Program. SN - 2666-6340 UR - https://www.unboundmedicine.com/medline/citation/32838362/Virus_Host_Interactome_and_Proteomic_Survey_Reveal_Potential_Virulence_Factors_Influencing_SARS_CoV_2_Pathogenesis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2666-6340(20)30015-5 DB - PRIME DP - Unbound Medicine ER -
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