SARS-CoV-2 infection impacts carbon metabolism and depends on glutamine for replication in Syrian hamster astrocytes.
Autor: | de Oliveira LG; Neuroimmune Interactions Laboratory, Institute of Biomedical Sciences, Department of Immunology, University of São Paulo, São Paulo, SP, Brazil.; Neuroimmunology of Arboviruses Laboratory, Scientific Platform Pasteur-USP, University of São Paulo, São Paulo, SP, Brazil., de Souza Angelo Y; Neuroimmune Interactions Laboratory, Institute of Biomedical Sciences, Department of Immunology, University of São Paulo, São Paulo, SP, Brazil.; Neuroimmunology of Arboviruses Laboratory, Scientific Platform Pasteur-USP, University of São Paulo, São Paulo, SP, Brazil., Yamamoto P; Neuroimmune Interactions Laboratory, Institute of Biomedical Sciences, Department of Immunology, University of São Paulo, São Paulo, SP, Brazil.; Neuroimmunology of Arboviruses Laboratory, Scientific Platform Pasteur-USP, University of São Paulo, São Paulo, SP, Brazil., Carregari VC; Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil., Crunfli F; Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil., Reis-de-Oliveira G; Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil., Costa L; Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil., Vendramini PH; Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil., Duque ÉA; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Dos Santos NB; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Firmino EM; Center for Research in Inflammatory Diseases (CRID), Department of Pharmacology-Ribeirão Preto Medical School-University of São Paulo, Ribeirão Preto, Brazil., Paiva IM; Center for Research in Inflammatory Diseases (CRID), Department of Pharmacology-Ribeirão Preto Medical School-University of São Paulo, Ribeirão Preto, Brazil., Almeida GM; Department of Biocehmistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Sebollela A; Department of Biocehmistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Polonio CM; Neuroimmune Interactions Laboratory, Institute of Biomedical Sciences, Department of Immunology, University of São Paulo, São Paulo, SP, Brazil.; Neuroimmunology of Arboviruses Laboratory, Scientific Platform Pasteur-USP, University of São Paulo, São Paulo, SP, Brazil., Zanluqui NG; Neuroimmune Interactions Laboratory, Institute of Biomedical Sciences, Department of Immunology, University of São Paulo, São Paulo, SP, Brazil.; Neuroimmunology of Arboviruses Laboratory, Scientific Platform Pasteur-USP, University of São Paulo, São Paulo, SP, Brazil., de Oliveira MG; Neuroimmune Interactions Laboratory, Institute of Biomedical Sciences, Department of Immunology, University of São Paulo, São Paulo, SP, Brazil., da Silva P; Neuroimmune Interactions Laboratory, Institute of Biomedical Sciences, Department of Immunology, University of São Paulo, São Paulo, SP, Brazil.; Neuroimmunology of Arboviruses Laboratory, Scientific Platform Pasteur-USP, University of São Paulo, São Paulo, SP, Brazil., Davanzo GG; Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil., Ayupe MC; Laboratory of Mucosal Immunology, Department of Immunology-Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil., Salgado CL; Laboratory of Mucosal Immunology, Department of Immunology-Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil., de Souza Filho AF; Laboratory of Applied Research in Mycobacteria, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil., de Araújo MV; Laboratory of Applied Research in Mycobacteria, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil., Silva-Pereira TT; Laboratory of Applied Research in Mycobacteria, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil., de Almeida Campos AC; Scientific Platform Pasteur - USP, University of São Paulo, São Paulo, SP, Brazil., Góes LGB; Scientific Platform Pasteur - USP, University of São Paulo, São Paulo, SP, Brazil., Dos Passos Cunha M; Scientific Platform Pasteur - USP, University of São Paulo, São Paulo, SP, Brazil., Caldini EG; Laboratory of Cellular Biology (LIM 59), School of Medicine, University of São Paulo, São Paulo, SP, Brazil., D'Império Lima MR; Department of Immunology, University of São Paulo, São Paulo, SP, Brazil., Fonseca DM; Laboratory of Mucosal Immunology, Department of Immunology-Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil., de Sá Guimarães AM; Laboratory of Applied Research in Mycobacteria, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil., Minoprio PC; Scientific Platform Pasteur - USP, University of São Paulo, São Paulo, SP, Brazil., Munhoz CD; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Mori CMC; Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo, São Paulo, SP, Brazil., Moraes-Vieira PM; Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil., Cunha TM; Center for Research in Inflammatory Diseases (CRID), Department of Pharmacology-Ribeirão Preto Medical School-University of São Paulo, Ribeirão Preto, Brazil., Martins-de-Souza D; Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil.; Experimental Medicine Research Cluster (EMRC), University of Campinas, Campinas, SP, Brazil.; D'Or Institute for Research and Education (IDOR), São Paulo, SP, Brazil.; Instituto Nacional de Biomarcadores em Neuropsiquiatria (INBION), Conselho Nacional de Desenvolvimento Científico e Tecnológico, São Paulo, SP, Brazil., Peron JPS; Neuroimmune Interactions Laboratory, Institute of Biomedical Sciences, Department of Immunology, University of São Paulo, São Paulo, SP, Brazil.; Neuroimmunology of Arboviruses Laboratory, Scientific Platform Pasteur-USP, University of São Paulo, São Paulo, SP, Brazil.; Immunopathology and Allergy Post Graduate Program, School of Medicine, University of São Paulo, São Paulo, SP, Brazil. |
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Jazyk: | angličtina |
Zdroj: | Journal of neurochemistry [J Neurochem] 2022 Oct; Vol. 163 (2), pp. 113-132. Date of Electronic Publication: 2022 Aug 15. |
DOI: | 10.1111/jnc.15679 |
Abstrakt: | COVID-19 causes more than million deaths worldwide. Although much is understood about the immunopathogenesis of the lung disease, a lot remains to be known on the neurological impact of COVID-19. Here, we evaluated immunometabolic changes using astrocytes in vitro and dissected brain areas of SARS-CoV-2 infected Syrian hamsters. We show that SARS-CoV-2 alters proteins of carbon metabolism, glycolysis, and synaptic transmission, many of which are altered in neurological diseases. Real-time respirometry evidenced hyperactivation of glycolysis, further confirmed by metabolomics, with intense consumption of glucose, pyruvate, glutamine, and alpha ketoglutarate. Consistent with glutamine reduction, the blockade of glutaminolysis impaired viral replication and inflammatory response in vitro. SARS-CoV-2 was detected in vivo in hippocampus, cortex, and olfactory bulb of intranasally infected animals. Our data evidence an imbalance in important metabolic molecules and neurotransmitters in infected astrocytes. We suggest this may correlate with the neurological impairment observed during COVID-19, as memory loss, confusion, and cognitive impairment. (© 2022 International Society for Neurochemistry.) |
Databáze: | MEDLINE |
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