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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
Li Jingjiao.
Guo Mingquan.
Tian Xiaoxu.
Liu Chengrong.
Wang Xin.
Yang Xing.
Wu Ping.
Xiao Zixuan.
Qu Yafei.
Yin Yue.
Fu Joyce.
Zhu Zhaoqin.
Liu Zhenshan.
Peng Chao.
Zhu Tongyu.
Liang Qiming.
Acceso Abierto
Atribución-NoComercial-SinDerivadas
10.1101/2020.03.31.019216
ABSTRACTThe 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.
www.biorxiv.org
2020
Artículo
https://www.biorxiv.org/content/biorxiv/early/2020/04/02/2020.03.31.019216.full.pdf
Inglés
VIRUS RESPIRATORIOS
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