Leveraging the antiviral type I interferon system as a first line of defense against SARS-CoV-2 pathogenicity

Daisy A. Hoagland, Rasmus Møller, Skyler A. Uhl, Kohei Oishi, Justin Frere, Ilona Golynker, Shu Horiuchi, Maryline Panis, Daniel Blanco-Melo, David Sachs, Knarik Arkun, Jean K. Lim, Benjamin R. tenOever

Research output: Contribution to journalArticlepeer-review

142 Scopus citations

Abstract

The emergence and spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in significant global morbidity, mortality, and societal disruption. A better understanding of virus-host interactions may potentiate therapeutic insights toward limiting this infection. Here we investigated the dynamics of the systemic response to SARS-CoV-2 in hamsters by histological analysis and transcriptional profiling. Infection resulted in consistently high levels of virus in the upper and lower respiratory tracts and sporadic occurrence in other distal tissues. A longitudinal cohort revealed a wave of inflammation, including a type I interferon (IFN-I) response, that was evident in all tissues regardless of viral presence but was insufficient to prevent disease progression. Bolstering the antiviral response with intranasal administration of recombinant IFN-I reduced viral disease, prevented transmission, and lowered inflammation in vivo. This study defines the systemic host response to SARS-CoV-2 infection and supports use of intranasal IFN-I as an effective means of early treatment.

Original languageEnglish
Pages (from-to)557-570.e5
JournalImmunity
Volume54
Issue number3
DOIs
StatePublished - 9 Mar 2021

Keywords

  • COVID-19
  • IFN-I
  • cytokine
  • hamster
  • intranasal
  • mRNA-seq
  • pandemic
  • prophylactic
  • therapeutic
  • transcriptomics

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