Experimental and natural evidence of SARS-CoV-2-infection-induced activation of type I interferon responses Academic Article uri icon

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abstract

  • Type I interferons (IFNs) are our first line of defense against virus infection. Recent studies have suggested the ability of SARS-CoV-2 proteins to inhibit IFN responses. Emerging data also suggest that timing and extent of IFN production is associated with manifestation of COVID-19 severity. In spite of progress in understanding how SARS-CoV-2 activates antiviral responses, mechanistic studies into wild-type SARS-CoV-2-mediated induction and inhibition of human type I IFN responses are scarce. Here we demonstrate that SARS-CoV-2 infection induces a type I IFN response in vitro and in moderate cases of COVID-19. In vitro stimulation of type I IFN expression and signaling in human airway epithelial cells is associated with activation of canonical transcriptions factors, and SARS-CoV-2 is unable to inhibit exogenous induction of these responses. Furthermore, we show that physiological levels of IFNα detected in patients with moderate COVID-19 is sufficient to suppress SARS-CoV-2 replication in human airway cells.

authors

  • Banerjee, Arinjay
  • El-Sayes, Nader
  • Budylowski, Patrick
  • Jacob, Rajesh Abraham
  • Richard, Daniel
  • Maan, Hassaan
  • Aguiar, Jennifer A
  • Demian, Wael L
  • Baid, Kaushal
  • D'Agostino, Michael R
  • Ang, Jann Catherine
  • Murdza, Tetyana
  • Tremblay, Benjamin J-M
  • Afkhami, Sam
  • Karimzadeh, Mehran
  • Irving, Aaron T
  • Yip, Lily
  • Ostrowski, Mario
  • Hirota, Jeremy
  • Kozak, Robert
  • Capellini, Terence D
  • Miller, Matthew S
  • Wang, Bo
  • Mubareka, Samira
  • McGeer, Allison J
  • McArthur, Andrew
  • Doxey, Andrew
  • Mossman, Karen

publication date

  • May 2021