# SARS-CoV-2 ORF7a Mutation Found in BF.5 and BF.7 Sublineages Impacts Its Functions

## TL;DR

A mutation in the ORF7a protein of SARS-CoV-2 Omicron subvariants BF.5 and BF.7 affects its ability to interfere with immune responses and hide from the immune system.

## Contribution

The study reveals that the H47Y mutation in ORF7a reduces its ability to block interferon and MHC-I, but not its anti-SERINC5 function.

## Key findings

- The H47Y mutation in ORF7a impairs its ability to antagonize the type I interferon response.
- The mutation also reduces ORF7a's ability to downregulate MHC-I cell surface levels.
- The anti-SERINC5 function of ORF7a remains unaffected by the H47Y mutation.

## 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 the ORF7a: H47Y mutation, in which the 47th residue of ORF7a has been mutated from a histidine (H) to a tyrosine (Y). Here, we evaluated the effect of this mutation on the three main functions ascribed to the SARS-CoV-2 ORF7a protein. Our findings show that H47Y mutation impairs the ability of SARS-CoV-2 ORF7a to antagonize the 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.