IFITM3 deficiency drives SARS-CoV-2 adaptation while preserving variant-specific traits.

ABSTRACT: SARS-CoV-2 can infect and adapt to multiple animal species, yet the host determinants that control interspecies viral adaptation remain poorly defined. Here we investigate whether interferon-induced transmembrane protein 3 (IFITM3), a key antiviral protein deficient in certain human populations, affects interspecies adaptation of SARS-CoV-2. We find that SARS-CoV-2 Beta and Omicron BA.4 variants passaged through IFITM3-deficient versus wild type mice exhibit enhanced replication and pathogenesis in this new host species. These enhancements are associated with amino acid substitutions in the viral genome, suggesting that IFITM3 limits accumulation of adaptive mutations. Mouse-adapted viruses enable comparative studies of variants in mice. Beta causes lung dysfunction and alters cilia-associ

SUBMITTER: Denz PJ 

PROVIDER: S-EPMC12917256 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature