Elevated ubiquitination contributes to protective immunity against severe SARS-CoV-2 infection

被引:9
作者
Che, Yinggang [1 ,2 ]
Jiang, Dongbo [1 ,3 ,7 ]
Zhang, Yong [2 ]
Zhang, Junqi [1 ]
Xu, Tianqi [2 ]
Sun, Yuanjie [1 ]
Fan, Jiangjiang [4 ]
Wang, Jiawei [1 ]
Chang, Ning [2 ]
Wu, Yingtong [5 ]
Yang, Shuya [1 ]
Xu, Leidi [2 ]
Ding, Jiaqi [1 ]
Hu, Chenchen [1 ]
Huang, Yinan [1 ]
Zhang, Jian [2 ,7 ]
Yang, Kun [1 ,3 ,6 ,7 ]
机构
[1] Fourth Mil Med Univ, Air Force Med Univ, Basic Med Sch, Dept Immunol, Xian, Shaanxi, Peoples R China
[2] Fourth Med Univ, Air Force Med Univ, Xijing Hosp, Dept Resp Med, Xian, Shaanxi, Peoples R China
[3] Fourth Mil Med Univ, Air Force Med Univ, Basic Med Sch, Key Lab Med Biohazard Prevent & Treatment Peoples, Xian, Shaanxi, Peoples R China
[4] Air Force Med Univ, Tangdu Hosp, Dept Thorac Surg, Xian, Shaanxi, Peoples R China
[5] First Sanat Air Force Healthcare Ctr Special Serv, Hangzhou, Zhejiang, Peoples R China
[6] Air Force Med Univ, Tangdu Hosp, Dept Rheumatol & Immunol, Xian, Shaanxi, Peoples R China
[7] Fourth Mil Med Univ, Air Force Med Univ, Basic Med Sch, Dept Immunol, Xian 86710032, Shaanxi, Peoples R China
基金
中国国家自然科学基金;
关键词
biomarker; immune system; prognosis; severe acute respiratory syndrome coronavirus 2; ubiquitination; CELLS;
D O I
10.1002/ctm2.1103
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BackgroundThe crosstalk between the ubiquitin-proteasome and the immune system plays an important role in the health and pathogenesis of viral infection. However, there have been few studies of ubiquitin activation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. MethodsWe investigated the effect of ubiquitination on SARS-CoV-2 infection and patient prognosis by integrating published coronavirus disease 2019 (COVID-19) multi-transcriptome data and bioinformatics methods. ResultsThe differential expression of COVID-19 samples revealed changed ubiquitination in most solid and hollow organs, and it was activated in lymphatic and other immune tissues. In addition, in the respiratory system of COVID-19 patients, the immune response was mainly focused on the alveoli, and the expression of ubiquitination reflected increasing immune infiltration. Ubiquitination stratification could significantly differentiate patients' prognosis and inflammation levels through the general transcriptional analysis of the peripheral blood of patients with COVID-19. Moreover, high ubiquitination levels were associated with a favourable prognosis, low inflammatory response, and reduced mechanical ventilation and intensive care unit. Moreover, high ubiquitination promoted a beneficial immune response while inhibiting immune damage. Finally, prognostic stratification and biomarker screening based on ubiquitination traits played an important role in clinical management and drug development. ConclusionUbiquitination characteristics provides new ideas for clinical intervention and prognostic guidance for COVID-19 patients.
引用
收藏
页数:18
相关论文
共 58 条
[1]   Household transmission of COVID-19 cases associated with SARS-CoV-2 delta variant (B.1.617.2): national case-control study [J].
Allen, Hester ;
Vusirikala, Amoolya ;
Flannagan, Joe ;
Twohig, Katherine A. ;
Zaidi, Asad ;
Chudasama, Dimple ;
Lamagni, Theresa ;
Groves, Natalie ;
Turner, Charlie ;
Rawlinson, Christopher ;
Lopez-Bernal, Jamie ;
Harris, Ross ;
Charlett, Andre ;
Dabrera, Gavin ;
Kall, Meaghan .
LANCET REGIONAL HEALTH-EUROPE, 2022, 12
[2]   xCell: digitally portraying the tissue cellular heterogeneity landscape [J].
Aran, Dvir ;
Hu, Zicheng ;
Butte, Atul J. .
GENOME BIOLOGY, 2017, 18
[3]   Discontinuation versus continuation of renin-angiotensin-system inhibitors in COVID-19 (ACEI-COVID): a prospective, parallel group, randomised, controlled, open-label trial [J].
Bauer, Axel ;
Schreinlechner, Michael ;
Sappler, Nikolay ;
Dolejsi, Theresa ;
Tilg, Herbert ;
Aulinger, Benedikt A. ;
Weiss, Guenter ;
Bellmann-Weiler, Rosa ;
Adolf, Christian ;
Wolf, Dominik ;
Pirklbauer, Markus ;
Graziadei, Ivo ;
Gaenzer, Hannes ;
von Bary, Christian ;
May, Andreas E. ;
Woell, Ewald ;
von Scheidt, Wolfgang ;
Rassaf, Tienush ;
Duerschmied, Daniel ;
Brenner, Christoph ;
Kaeaeb, Stefan ;
Metzler, Bernhard ;
Joannidis, Michael ;
Kain, Hans-Ulrich ;
Kaiser, Norbert ;
Schwinger, Robert ;
Witzenbichler, Bernhard ;
Alber, Hannes ;
Straube, Florian ;
Hartmann, Niels ;
Achenbach, Stephan ;
von Bergwelt-Baildon, Michael ;
von Stuelpnagel, Lukas ;
Schoenherr, Sebastian ;
Forer, Lukas ;
Embacher-Aichhorn, Sabine ;
Mansmann, Ulrich ;
Rizzast, Konstantinos D. ;
Massberg, Steffen .
LANCET RESPIRATORY MEDICINE, 2021, 9 (08) :863-872
[4]   Ubiquitin Ligase Redundancy and Nuclear-Cytoplasmic Localization in Yeast Protein Quality Control [J].
Breckel, Carolyn Allain ;
Hochstrasser, Mark .
BIOMOLECULES, 2021, 11 (12)
[5]   Modeling insights into SARS-CoV-2 respiratory tract infections prior to immune protection [J].
Chen, Alexander ;
Wessler, Timothy ;
Daftari, Katherine ;
Hinton, Kameryn ;
Boucher, Richard C. ;
Pickles, Raymond ;
Freeman, Ronit ;
Lai, Samuel K. ;
Forest, M. Gregory .
BIOPHYSICAL JOURNAL, 2022, 121 (09) :1619-1631
[6]   Clinical and immunological features of severe and moderate coronavirus disease 2019 [J].
Chen, Guang ;
Wu, Di ;
Guo, Wei ;
Cao, Yong ;
Huang, Da ;
Wang, Hongwu ;
Wang, Tao ;
Zhang, Xiaoyun ;
Chen, Huilong ;
Yu, Haijing ;
Zhang, Xiaoping ;
Zhang, Minxia ;
Wu, Shiji ;
Song, Jianxin ;
Chen, Tao ;
Han, Meifang ;
Li, Shusheng ;
Luo, Xiaoping ;
Zhao, Jianping ;
Ning, Qin .
JOURNAL OF CLINICAL INVESTIGATION, 2020, 130 (05) :2620-2629
[7]   Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England [J].
Davies, Nicholas G. ;
Abbott, Sam ;
Barnard, Rosanna C. ;
Jarvis, Christopher, I ;
Kucharski, Adam J. ;
Munday, James D. ;
Pearson, Carl A. B. ;
Russell, Timothy W. ;
Tully, Damien C. ;
Washburne, Alex D. ;
Wenseleers, Tom ;
Gimma, Amy ;
Waites, William ;
Wong, Kerry L. M. ;
van Zandvoort, Kevin ;
Silverman, Justin D. ;
Diaz-Ordaz, Karla ;
Keogh, Ruth ;
Eggo, Rosalind M. ;
Funk, Sebastian ;
Jit, Mark ;
Atkins, Katherine E. ;
Edmunds, W. John .
SCIENCE, 2021, 372 (6538) :149-+
[8]   Quantitative Proteomic Atlas of Ubiquitination and Acetylation in the DNA Damage Response [J].
Elia, Andrew E. H. ;
Boardman, Alexander P. ;
Wang, David C. ;
Huttlin, Edward L. ;
Everley, Robert A. ;
Dephoure, Noah ;
Zhou, Chunshui ;
Koren, Itay ;
Gygi, Steven P. ;
Elledge, Stephen J. .
MOLECULAR CELL, 2015, 59 (05) :867-881
[9]  
Faria NR, 2021, SCIENCE, V372, P815, DOI [10.1126/science.abh2644, 10.1101/2021.02.26.21252554, 10.1126/science.abh2644Article]
[10]   Cullin Ring Ubiquitin Ligases (CRLs) in Cancer: Responses to Ionizing Radiation (IR) Treatment [J].
Fouad, Shahd ;
Wells, Owen S. ;
Hill, Mark A. ;
D'Angiolella, Vincenzo .
FRONTIERS IN PHYSIOLOGY, 2019, 10