ABSTRACT In this study, the infection dynamics, replication, and pathogenicity of a recombinant virus containing a deletion of ORF6 (rWA1ΔORF6) on the backbone of the highly virulent SARS-CoV-2 WA1 virus (rWA1) were investigated and compared to the parental rWA1 virus. While both rWA1 and rWA1ΔORF6 viruses replicated efficiently in cultured cells , the rWA1ΔORF6 virus produced smaller plaques, suggesting reduced cell-to-cell spread. Luciferase reporter assays revealed immune-suppressing effects of ORF6 on interferon (IFN) and nuclear factor kappa B (NF-κB) signaling pathways. Pathogenesis assessment in cats revealed that animals inoculated with rWA1 were lethargic and presented with fever on days 2 and 4 post-infection (pi), whereas rWA1ΔORF6-inoculated animals developed subclinical infection . Additionally, animals inoculated with rWA1ΔORF6 presented reduced infectious virus shedding in nasal and oral secretions and broncho-alveolar lavage fluid when compared with the rWA1-inocu...
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