SARS-CoV-2 Variants Show Different Host Cell Proteome Profiles With Delayed Immune Response Activation in Omicron-Infected Cells

Interferon signaling in the nasal epithelium distinguishes among lethal and common cold respiratory viruses and is critical for viral clearance

“…Indeed, the still-dominant omicron variant replicates more rapidly in upper airway models and seems to replicate less efficiently than early SARS-CoV-2 isolates in lung-derived epithelial cell lines such as Calu3 and lower airway ALI cultures 64,86,87 . Though the degree of IFN induction during omicron infection relative to early SARS-CoV-2 isolates is a topic of debate 88,89 , a consensus has emerged in the literature that suggests SARS-CoV-2 VOCs (and especially omicron BA.1) have enhanced IFN resistance, which is consistent with our data 87,90–92 . This reduced IFN sensitivity likely explains the lack of clearance and temperature sensitivity observed during omicron BA.1 infection in our nasal cell model, which parallels our observations during IAV infection.…”

“…88,89 , a consensus has emerged in the literature that suggests SARS-CoV-2 VOCs (and especially omicron BA.1) Leveraging a primary nasal cell model to compare respiratory viruses associated with a range of clinical pathologies, we propose that common cold-associated viruses induce temperatureregulated IFN responses that restrict viral replication. IFN antagonism by lethal HCoVs and reduced IFN sensitivity in the case of IAV and the omicron BA.1 variant of SARS-CoV-2 hinder viral clearance in nasal cell cultures.…”