Selected article for: "immune system and viral load"
Author: Maktura, Grazielle Celeste; Dias, Thomaz Luscher; Zambalde, Érika Pereira; Brenha, Bianca; Amorim, Mariene R.; Santos, Luana Nunes; Buscaratti, Lucas; de Angeli Elston, João Gabriel; Mara, Cynthia; Mancini, Mariana Camargo Silva; Pavan, Isadora Carolina Betim; Toledo-Teixeira, Daniel A.; Bispo-dos-Santos, Karina; Parise, Pierina L.; Muraro, Stefanie Primon; de Souza, Gabriela Fabiano; Morelli, Ana Paula; da Silva, Luiz Guilherme Salvino; de Castro, Ícaro Maia Santos; Barbosa, Guilherme O.; Ludwig, Raissa G.; Knittel, Thiago L.; Saccon, Tatiana D.; Mori, Marcelo A.; Granja, Fabiana; Carvalho, Hernandes F.; da Silva, Luis Lamberti Pinto; Nakaya, Helder I.; Proenca-Modena, Jose Luiz; Simabuco, Fernando Moreira; Marques-Souza, Henrique
Title: Increased mTOR signaling, impaired autophagic flux and cell-to-cell viral transmission are hallmarks of SARS-CoV-2 infection
  • Cord-id: uaqtr0z7
  • Document date: 2021_10_14
    • ID: uaqtr0z7
    Snippet: The COVID-19 disease caued by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has two characteristics that distinguish it from other viral infections. It affects more severely people with pre-existing comorbidities and viral load peaks prior to the onset of the symptoms. Investigating factors that could contribute to these characteristics, we found increased mTOR signaling and suppressed genes related to autophagy, lysosome, and vesicle fusion in Vero E6 cells infected with SARS
    Document: The COVID-19 disease caued by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has two characteristics that distinguish it from other viral infections. It affects more severely people with pre-existing comorbidities and viral load peaks prior to the onset of the symptoms. Investigating factors that could contribute to these characteristics, we found increased mTOR signaling and suppressed genes related to autophagy, lysosome, and vesicle fusion in Vero E6 cells infected with SARS-CoV-2. Transcriptomic data mining of bronchoalveolar epithelial cells from severe COVID-19 patients revealed that COVID-19 severity is associated with increased expression of genes related to mTOR signaling and decreased expression of genes related to autophagy, lysosome function, and vesicle fusion. SARS-CoV-2 infection in Vero E6 cells also resulted in virus retention inside the cells and trafficking of virus-bearing vesicles between neighboring cells. Our findings support a scenario where SARS-CoV-2 benefits from compromised autophagic flux and inhibited exocytosis in individuals with chronic hyperactivation of mTOR signaling, which might relate to undetectable proliferation and evasion of the immune system.

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