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10.1038/s41598-022-10763-2

http://scihub22266oqcxt.onion/10.1038/s41598-022-10763-2
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35484173!9048621!35484173
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suck abstract from ncbi


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pmid35484173      Sci+Rep 2022 ; 12 (1): 6972
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  • Airway epithelial interferon response to SARS-CoV-2 is inferior to rhinovirus and heterologous rhinovirus infection suppresses SARS-CoV-2 replication #MMPMID35484173
  • Vanderwall ER; Barrow KA; Rich LM; Read DF; Trapnell C; Okoloko O; Ziegler SF; Hallstrand TS; White MP; Debley JS
  • Sci Rep 2022[Apr]; 12 (1): 6972 PMID35484173show ga
  • Common alphacoronaviruses and human rhinoviruses (HRV) induce type I and III interferon (IFN) responses important to limiting viral replication in the airway epithelium. In contrast, highly pathogenic betacoronaviruses including SARS-CoV-2 may evade or antagonize RNA-induced IFN I/III responses. In airway epithelial cells (AECs) from children and older adults we compared IFN I/III responses to SARS-CoV-2 and HRV-16, and assessed whether pre-infection with HRV-16, or pretreatment with recombinant IFN-beta or IFN-lambda, modified SARS-CoV-2 replication. Bronchial AECs from children (ages 6-18 years) and older adults (ages 60-75 years) were differentiated ex vivo to generate organotypic cultures. In a biosafety level 3 (BSL-3) facility, cultures were infected with SARS-CoV-2 or HRV-16, and RNA and protein was harvested from cell lysates 96 h. following infection and supernatant was collected 48 and 96 h. following infection. In additional experiments cultures were pre-infected with HRV-16, or pre-treated with recombinant IFN-beta1 or IFN-lambda2 before SARS-CoV-2 infection. In a subset of experiments a range of infectious concentrations of HRV-16, SARS-CoV-2 WA-01, SARS-CoV-2 Delta variant, and SARS-CoV-2 Omicron variant were studied. Despite significant between-donor heterogeneity SARS-CoV-2 replicated 100 times more efficiently than HRV-16. IFNB1, INFL2, and CXCL10 gene expression and protein production following HRV-16 infection was significantly greater than following SARS-CoV-2. IFN gene expression and protein production were inversely correlated with SARS-CoV-2 replication. Treatment of cultures with recombinant IFNbeta1 or IFNlambda2, or pre-infection of cultures with HRV-16, markedly reduced SARS-CoV-2 replication. In addition to marked between-donor heterogeneity in IFN responses and viral replication, SARS-CoV-2 (WA-01, Delta, and Omicron variants) elicits a less robust IFN response in primary AEC cultures than does rhinovirus, and heterologous rhinovirus infection, or treatment with recombinant IFN-beta1 or IFN-lambda2, reduces SARS-CoV-2 replication, although to a lesser degree for the Delta and Omicron variants.
  • |*COVID-19 Drug Treatment[MESH]
  • |*Interferons/pharmacology[MESH]
  • |Adolescent[MESH]
  • |Aged[MESH]
  • |Antiviral Agents[MESH]
  • |Child[MESH]
  • |Humans[MESH]
  • |Middle Aged[MESH]
  • |RNA[MESH]
  • |Rhinovirus[MESH]


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