SARS-CoV-2 ORF8 accessory protein is a virulence factor.

According to log-rank test, the most virulent phenotypes (SARS-CoV-2-WT and SARS-CoV-2-∆6) show a highly significant (** P < 0.01) reduced survival as compared to mock-infected mice, while partially attenuated mutants (SARS-CoV-2-∆7ab, SARS-CoV-2-∆8, and SARS-CoV-2-∆[6,8]) just showed significant differences (* P < 0.05) in relation to mock infection.

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SARS-CoV-2-Δ8 infection showed a trend of increasing IFN signaling (IFNλ3, interferon-stimulated gene [ISG15], and MX1, P values 0.4337, 0.1126, and 0.2285, respectively) as compared to WT at 3 dpi, while reducing IFN-stimulated gene levels (IFNλ3, ISG15, IFIT1, OAS1, and XAF1) at 6 dpi.

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