Contribution of SARS-CoV-2 accessory proteins to viral pathogenicity in K18 hACE2 transgenic mice

By using a reverse genetics system, recombinant SARS-CoV-2 lacking viral ORF 3a, 6, 7a, 7b and 8, many of which are involved in antagonizing for host immune responses, were generated. Infection of these viruses in hACE2 transgenic mice revealed that ORF3a and ORF6 are the major contributors of viral pathogenesis, while ORF7a, 7b and 8 have little impact on disease outcome.