Integrative systems immunology uncovers molecular networks of the cell cycle that stratify COVID-19 severity.

Autor: Prado CAS; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil., Fonseca DLM; Interunit Postgraduate Program on Bioinformatics, Institute of Mathematics and Statistics (IME), University of Sao Paulo (USP), Sao Paulo, Brazil., Singh Y; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil., Filgueiras IS; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Baiocchi GC; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Plaça DR; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil., Marques AHC; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil., Dantas-Komatsu RCS; Postgraduate Program in Health Sciences, Federal University of Rio Grande do Norte, Natal, Brazil., Usuda JN; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil., Freire PP; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Salgado RC; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Napoleao SMDS; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Ramos RN; Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31), Departament of Hematology and Cell Therapy, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, University of São Paulo, São Paulo, Brazil.; Instituto D'Or de Ensino e Pesquisa, Hospital São Luiz, São Paulo, Brazil., Rocha V; Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31), Departament of Hematology and Cell Therapy, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, University of São Paulo, São Paulo, Brazil.; Instituto D'Or de Ensino e Pesquisa, Hospital São Luiz, São Paulo, Brazil.; Fundação Pró-Sangue-Hemocentro de São Paulo, Hospital das Clínicas da Universidade de São Paulo, São Paulo, Brazil.; Department of Hematology, Churchill Hospital, University of Oxford, Oxford, UK., Zhou G; Institute of Parasitology, McGill University, Montreal, Quebec, Canada., Catar R; Department of Nephrology and Internal Intensive Care Medicine, Charité University Hospital, Berlin, Germany., Moll G; Department of Nephrology and Internal Intensive Care Medicine, Charité University Hospital, Berlin, Germany.; Berlin Institute of Health (BIH) and Berlin Center for Regenerative Therapies (BCRT), Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin-Brandenburg School for Regenerative Therapies (BSRT), all Charité Universitätsmedizin Berlin, Berlin, Germany., Camara NOS; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., de Miranda GC; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Calich VLG; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Giil LM; Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway., Mishra N; Institute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, Kiel, Germany., Tran F; Institute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, Kiel, Germany.; Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel, Germany., Luchessi AD; Department of Clinical and Toxicology Analysis, Federal University of Rio Grande do Norte, Natal, Brazil., Nakaya HI; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.; Instituto Israelita de Ensino e Pesquisa Albert Einstein, Hospital Israelita Albert Einstein, São Paulo, Brazil., Ochs HD; Department of Pediatrics, University of Washington School of Medicine and Seattle Children's Research Institute, Seattle, Washington, USA., Jurisica I; Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute, UHN, Toronto, Ontario, Canada.; Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia.; Departments of Medical Biophysics and Computer Science, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.; Krembil Research Institute, UHN, Data Science Discovery Centre, Toronto, Ontario, Canada., Schimke LF; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Cabral-Marques O; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.; Interunit Postgraduate Program on Bioinformatics, Institute of Mathematics and Statistics (IME), University of Sao Paulo (USP), Sao Paulo, Brazil.; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.; Department of Pharmacy and Postgraduate Program of Health and Science, Federal University of Rio Grande do Norte, Natal, Brazil.; Department of Medicine, Division of Molecular Medicine, University of São Paulo School of Medicine, São Paulo, Brazil.; Laboratory of Medical Investigation 29, University of São Paulo School of Medicine, São Paulo, Brazil.
Jazyk: angličtina
Zdroj: Journal of medical virology [J Med Virol] 2023 Feb; Vol. 95 (2), pp. e28450.
DOI: 10.1002/jmv.28450
Abstrakt: Several perturbations in the number of peripheral blood leukocytes, such as neutrophilia and lymphopenia associated with Coronavirus disease 2019 (COVID-19) severity, point to systemic molecular cell cycle alterations during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, the landscape of cell cycle alterations in COVID-19 remains primarily unexplored. Here, we performed an integrative systems immunology analysis of publicly available proteome and transcriptome data to characterize global changes in the cell cycle signature of COVID-19 patients. We found significantly enriched cell cycle-associated gene co-expression modules and an interconnected network of cell cycle-associated differentially expressed proteins (DEPs) and genes (DEGs) by integrating the molecular data of 1469 individuals (981 SARS-CoV-2 infected patients and 488 controls [either healthy controls or individuals with other respiratory illnesses]). Among these DEPs and DEGs are several cyclins, cell division cycles, cyclin-dependent kinases, and mini-chromosome maintenance proteins. COVID-19 patients partially shared the expression pattern of some cell cycle-associated genes with other respiratory illnesses but exhibited some specific differential features. Notably, the cell cycle signature predominated in the patients' blood leukocytes (B, T, and natural killer cells) and was associated with COVID-19 severity and disease trajectories. These results provide a unique global understanding of distinct alterations in cell cycle-associated molecules in COVID-19 patients, suggesting new putative pathways for therapeutic intervention.
(© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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