| First Author | Willett JDS | Year | 2024 |
| Journal | Commun Biol | Volume | 7 |
| Issue | 1 | Pages | 191 |
| PubMed ID | 38365933 | Mgi Jnum | J:349961 |
| Mgi Id | MGI:7606469 | Doi | 10.1038/s42003-024-05878-3 |
| Citation | Willett JDS, et al. (2024) SARS-CoV-2 rapidly evolves lineage-specific phenotypic differences when passaged repeatedly in immune-naive mice. Commun Biol 7(1):191 |
| abstractText | The persistence of SARS-CoV-2 despite the development of vaccines and a degree of herd immunity is partly due to viral evolution reducing vaccine and treatment efficacy. Serial infections of wild-type (WT) SARS-CoV-2 in Balb/c mice yield mouse-adapted strains with greater infectivity and mortality. We investigate if passaging unmodified B.1.351 (Beta) and B.1.617.2 (Delta) 20 times in K18-ACE2 mice, expressing the human ACE2 receptor, in a BSL-3 laboratory without selective pressures, drives human health-relevant evolution and if evolution is lineage-dependent. Late-passage virus causes more severe disease, at organism and lung tissue scales, with late-passage Delta demonstrating antibody resistance and interferon suppression. This resistance co-occurs with a de novo spike S371F mutation, linked with both traits. S371F, an Omicron-characteristic mutation, is co-inherited at times with spike E1182G per Nanopore sequencing, existing in different within-sample viral variants at others. Both S371F and E1182G are linked to mammalian GOLGA7 and ZDHHC5 interactions, which mediate viral-cell entry and antiviral response. This study demonstrates SARS-CoV-2's tendency to evolve with phenotypic consequences, its evolution varying by lineage, and suggests non-dominant quasi-species contribution. |
