Accelerated Adaptation of SARS-CoV-2 Variants in Mice Lacking IFITM3 Preserves Distinct Tropism and Pathogenesis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

ABSTRACT Here we investigated whether interferon induced transmembrane protein 3 (IFITM3), a key antiviral deficient in certain human populations, affects interspecies adaptation of SARS-CoV-2. We found that SARS-CoV-2 Beta and Omicron variants passaged through IFITM3-deficient versus wild type mice exhibit enhanced replication pathogenesis this new host species. Enhancements associated with amino acid substitutions the viral genome, suggesting IFITM3 limits accumulation adaptive mutations. Mouse-adapted viruses enabled comparative studies mice. caused lung dysfunction altered cilia-associated gene programs, consistent broad antigen distribution lungs. Omicron, which shows low pathogenicity upper respiratory tract preference humans, replicated to high nasal titers while showing restrained spatial lungs diminished inflammatory responses compared Beta. Our findings demonstrate deficiency accelerates coronavirus reveal intrinsic variant traits shape tropism, immunity, across hosts. HIGHLIGHTS is critical barrier species strains enable pathology favors nose large airways, leading mild exhibits replication, driving severe inflammation

Language: Английский

Link of TMPRSS2 expression with tumor immunogenicity and response to immune checkpoint inhibitors in cancers

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 7, 2025

Language: Английский