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Basic Characteristics of Mutations
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Mutation Site
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A892V |
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Mutation Site Sentence
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While only S371F and A892V were observed to have the same allele frequency in P13 with E1182G not detected by Nanopore in this passage, but detected by Illumina, this could be a product of sequencing error or changes, alongside observing co-inheritance of alleles at distinct times in distinct samples (Fig. 8). |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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S |
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Standardized Encoding Gene
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S
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Genotype/Subtype
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Delta |
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Viral Reference
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NC_045512.2
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Functional Impact and Mechanisms
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Disease
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COVID-19
Cell line
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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38365933
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Title
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SARS-CoV-2 rapidly evolves lineage-specific phenotypic differences when passaged repeatedly in immune-naive mice
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Author
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Willett JDS,Gravel A,Dubuc I,Gudimard L,Dos Santos Pereira Andrade AC,Lacasse E,Fortin P,Liu JL,Cervantes JA,Galvez JH,Djambazian HHV,Zwaig M,Roy AM,Lee S,Chen SH,Ragoussis J,Flamand L
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Journal
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Communications biology
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Journal Info
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2024 Feb 16;7(1):191
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Abstract
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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.
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Sequence Data
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-
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