tetano
Editor, Senior Moderator
Immunity
. 2021 Jan 29;S1074-7613(21)00040-6.
doi: 10.1016/j.immuni.2021.01.017. Online ahead of print.
Leveraging the antiviral type I interferon system as a first line of defense against SARS-CoV-2 pathogenicity
Daisy A Hoagland[SUP] 1 [/SUP], Rasmus M?ller[SUP] 1 [/SUP], Skyler A Uhl[SUP] 1 [/SUP], Kohei Oishi[SUP] 1 [/SUP], Justin Frere[SUP] 1 [/SUP], Ilona Golynker[SUP] 1 [/SUP], Shu Horiuchi[SUP] 1 [/SUP], Maryline Panis[SUP] 1 [/SUP], Daniel Blanco-Melo[SUP] 1 [/SUP], David Sachs[SUP] 2 [/SUP], Knarik Arkun[SUP] 3 [/SUP], Jean K Lim[SUP] 1 [/SUP], Benjamin R tenOever[SUP] 4 [/SUP]
Affiliations
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.
Keywords: COVID-19; IFN-I; cytokine; hamster; intranasal; mRNA-seq; pandemic; prophylactic; therapeutic; transcriptomics.
. 2021 Jan 29;S1074-7613(21)00040-6.
doi: 10.1016/j.immuni.2021.01.017. Online ahead of print.
Leveraging the antiviral type I interferon system as a first line of defense against SARS-CoV-2 pathogenicity
Daisy A Hoagland[SUP] 1 [/SUP], Rasmus M?ller[SUP] 1 [/SUP], Skyler A Uhl[SUP] 1 [/SUP], Kohei Oishi[SUP] 1 [/SUP], Justin Frere[SUP] 1 [/SUP], Ilona Golynker[SUP] 1 [/SUP], Shu Horiuchi[SUP] 1 [/SUP], Maryline Panis[SUP] 1 [/SUP], Daniel Blanco-Melo[SUP] 1 [/SUP], David Sachs[SUP] 2 [/SUP], Knarik Arkun[SUP] 3 [/SUP], Jean K Lim[SUP] 1 [/SUP], Benjamin R tenOever[SUP] 4 [/SUP]
Affiliations
- PMID: 33577760
- PMCID: PMC7846242
- DOI: 10.1016/j.immuni.2021.01.017
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.
Keywords: COVID-19; IFN-I; cytokine; hamster; intranasal; mRNA-seq; pandemic; prophylactic; therapeutic; transcriptomics.