Key result
Pre-infection of airway epithelial cultures with HRV-16 markedly reduced SARS-CoV-2 replication from a median copy number of 267,264 to 14,788.
Why the study?
Common respiratory viruses induce protective interferon responses, but highly pathogenic betacoronaviruses including SARS-CoV-2 may evade or antagonize RNA-induced type I and III interferon responses in airway epithelium.
Does pre-infection with rhinovirus or treatment with recombinant interferon reduce SARS-CoV-2 replication in human airway epithelial cells?
Does pre-infection with rhinovirus or treatment with recombinant interferon reduce SARS-CoV-2 replication in human airway epithelial cells?
SARS-CoV-2 elicits a blunted interferon response compared to rhinovirus in human airway epithelial cells, and augmenting this response via heterologous rhinovirus infection or exogenous interferon significantly suppresses SARS-CoV-2 replication.
Should not yet change COVID-19 management; leaves open whether rhinovirus-induced interferon responses can be harnessed therapeutically.
Introduction 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. Methods 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-β or IFN-λ, modified SARS-CoV-2 replication. Bronchial AECs from children (ages 6-18 yrs.) and older adults (ages 60-75 yrs.) 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 hrs. following infection and supernatant was collected 48 and 96 hrs. following infection. In additional experiments cultures were pre-infected with HRV-16, or pre-treated with recombinant IFN-β1 or IFN-λ2 before SARS-CoV-2 infection. Results 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 IFNβ1 or IFNλ2, or pre-infection of cultures with HRV-16, markedly reduced SARS-CoV-2 replication. Discussion In addition to marked between-donor heterogeneity in IFN responses and viral replication, SARS-CoV-2 elicits a less robust IFN response in primary AEC cultures than does rhinovirus, and heterologous rhinovirus infection, or treatment with recombinant IFN-β1 or IFN-λ2, markedly reduces SARS-CoV-2 replication.
No takes yet. Share an insight, caveat, or question.
Vanderwall et al. (2021) studied SARS-CoV-2 infection (n=25). HRV-16 pre-infection vs. SARS-CoV-2 infection alone was evaluated on SARS-CoV-2 replication (median viral copy number) (p=0.002). Pre-infection of airway epithelial cultures with HRV-16 markedly reduced SARS-CoV-2 replication from a median copy number of 267,264 to 14,788.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: