SARS-CoV-2 ORF7a mutation found in BF.5 and BF.7 sublineages impacts its functions

ABSTRACT A feature of the SARS-CoV-2 Omicron subvariants BF.5 and BF.7 that recently circulated mainly in China and Japan was the high prevalence of ORF7a: H47Y mutation. Here we evaluated the effect of this mutation on the three main functions ascribed to SARS-CoV-2 ORF7a protein. Our findings show that H47Y mutation impairs the ability of SARS-CoV-2 ORF7a to antagonize type-I interferon (IFN-I) response and to downregulate Major Histocompatibility Complex-I (MHC-I) cell surface levels, but had no effect in its anti-SERINC5 function. Overall, our results suggest that the H47Y mutation of ORF7a affects important functions of this protein resulting in changes in virus pathogenesis. Importance In late 2021, the Omicron (B.1.1.529) VOC emerged and outcompeted the circulating VOC Delta (B.1.617.2). Soon afterwards, Omicron VOC has expanded and diversified in the world. Among the emerged subvariants of Omicron are BF.5 and BF.7 that are characterized by the presence of a number of mutations across their genome and spread quite effectively across China and other countries later on. One such mutation that was found in the vast majority of isolates of the BF.5 and BF.7 subvariants was ORF7a: H47Y, whose effect on ORF7a is unknown. In this report, we show that H47Y inhibits a number of ORF7a functions, which can potentially affect virus pathogenesis.