RNA-seq time-course of Calu-3 cells infected with SARS-CoV-2 early-lineage and Alpha variant viruses

Emergence of SARS-CoV-2 variants of concern (VOCs), including the globally successful Alpha (B.1.1.7) variant, suggests viral adaptation to enhance human-to-human transmission. Although much effort has focused on characterisation of spike changes, Alpha mutations outside spike likely contribute to adaptation. Here we used RNAseq as well as viral replication assays to show that Alpha isolates more effectively suppress innate immune responses (ISGs as assessed by RNA) in airway epithelial cells, compared to first wave isolates. We found that Alpha has dramatically increased subgenomic RNA and protein levels of N, Orf9b and Orf6, all known innate immune antagonists.