Current Issues in Molecular Biology (Dec 2022)
Increased mTOR Signaling and Impaired Autophagic Flux Are Hallmarks of SARS-CoV-2 Infection
- Érika Pereira Zambalde,
- Thomaz Luscher Dias,
- Grazielle Celeste Maktura,
- Mariene R. Amorim,
- Bianca Brenha,
- Luana Nunes Santos,
- Lucas Buscaratti,
- João Gabriel de Angeli Elston,
- Mariana Camargo Silva Mancini,
- Isadora Carolina Betim Pavan,
- Daniel A. Toledo-Teixeira,
- Karina Bispo-dos-Santos,
- Pierina L. Parise,
- Ana Paula Morelli,
- Luiz Guilherme Salvino da Silva,
- Ícaro Maia Santos de Castro,
- Tatiana D. Saccon,
- Marcelo A. Mori,
- Fabiana Granja,
- Helder I. Nakaya,
- Jose Luiz Proenca-Modena,
- Henrique Marques-Souza,
- Fernando Moreira Simabuco
Affiliations
- Érika Pereira Zambalde
- Multidisciplinary Laboratory of Food and Health (LabMAS), School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira 13484-350, SP, Brazil
- Thomaz Luscher Dias
- Computational Systems Biology Lab (CSBL), Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo 05508-000, SP, Brazil
- Grazielle Celeste Maktura
- Brazilian Laboratory on Silencing Technologies (BLaST), Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas 13083-872, SP, Brazil
- Mariene R. Amorim
- Brazilian Laboratory on Silencing Technologies (BLaST), Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas 13083-872, SP, Brazil
- Bianca Brenha
- Brazilian Laboratory on Silencing Technologies (BLaST), Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas 13083-872, SP, Brazil
- Luana Nunes Santos
- Brazilian Laboratory on Silencing Technologies (BLaST), Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas 13083-872, SP, Brazil
- Lucas Buscaratti
- Brazilian Laboratory on Silencing Technologies (BLaST), Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas 13083-872, SP, Brazil
- João Gabriel de Angeli Elston
- Brazilian Laboratory on Silencing Technologies (BLaST), Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas 13083-872, SP, Brazil
- Mariana Camargo Silva Mancini
- Multidisciplinary Laboratory of Food and Health (LabMAS), School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira 13484-350, SP, Brazil
- Isadora Carolina Betim Pavan
- Multidisciplinary Laboratory of Food and Health (LabMAS), School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira 13484-350, SP, Brazil
- Daniel A. Toledo-Teixeira
- Laboratory of Emerging Viruses (LEVE), Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas 13083-872, SP, Brazil
- Karina Bispo-dos-Santos
- Laboratory of Emerging Viruses (LEVE), Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas 13083-872, SP, Brazil
- Pierina L. Parise
- Laboratory of Emerging Viruses (LEVE), Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas 13083-872, SP, Brazil
- Ana Paula Morelli
- Multidisciplinary Laboratory of Food and Health (LabMAS), School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira 13484-350, SP, Brazil
- Luiz Guilherme Salvino da Silva
- Multidisciplinary Laboratory of Food and Health (LabMAS), School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira 13484-350, SP, Brazil
- Ícaro Maia Santos de Castro
- Computational Systems Biology Lab (CSBL), Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo 05508-000, SP, Brazil
- Tatiana D. Saccon
- Experimental Medicine Research Cluster (EMRC), University of Campinas (UNICAMP), Campinas 13083-872, SP, Brazil
- Marcelo A. Mori
- Experimental Medicine Research Cluster (EMRC), University of Campinas (UNICAMP), Campinas 13083-872, SP, Brazil
- Fabiana Granja
- Laboratory of Emerging Viruses (LEVE), Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas 13083-872, SP, Brazil
- Helder I. Nakaya
- Computational Systems Biology Lab (CSBL), Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo 05508-000, SP, Brazil
- Jose Luiz Proenca-Modena
- Laboratory of Emerging Viruses (LEVE), Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas (UNICAMP), Campinas 13083-872, SP, Brazil
- Henrique Marques-Souza
- Brazilian Laboratory on Silencing Technologies (BLaST), Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas 13083-872, SP, Brazil
- Fernando Moreira Simabuco
- Multidisciplinary Laboratory of Food and Health (LabMAS), School of Applied Sciences (FCA), University of Campinas (UNICAMP), Limeira 13484-350, SP, Brazil
- DOI
- https://doi.org/10.3390/cimb45010023
- Journal volume & issue
-
Vol. 45,
no. 1
pp. 327 – 336
Abstract
The COVID-19 (Coronavirus Disease 2019), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), severely affects mainly individuals with pre-existing comorbidities. Here our aim was to correlate the mTOR (mammalian/mechanistic Target of Rapamycin) and autophagy pathways with the disease severity. Through western blotting and RNA analysis, we found increased mTOR signaling and suppression of genes related to autophagy, lysosome, and vesicle fusion in Vero E6 cells infected with SARS-CoV-2 as well as in transcriptomic data mining of bronchoalveolar epithelial cells from severe COVID-19 patients. Immunofluorescence co-localization assays also indicated that SARS-CoV-2 colocalizes within autophagosomes but not with a lysosomal marker. Our findings indicate that SARS-CoV-2 can benefit from compromised autophagic flux and inhibited exocytosis in individuals with chronic hyperactivation of mTOR signaling.
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