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Basic Characteristics of Mutations
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Mutation Site
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R203K |
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Mutation Site Sentence
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Recreating a mutation found in the alpha and omicron variants in an early pandemic (WA-1) background, we find that the R203K+G204R mutation is sufficient to enhance replication, fitness, and pathogenesis of SARS-CoV-2. |
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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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Standardized Encoding Gene
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Genotype/Subtype
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- |
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Viral Reference
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MN985325.1;MN996532.2;MT121216.1;AY278741.1;KF367457.1
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Functional Impact and Mechanisms
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Disease
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-
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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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America |
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Literature Information
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PMID
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35728038
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Title
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Nucleocapsid mutations in SARS-CoV-2 augment replication and pathogenesis
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Author
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Johnson BA,Zhou Y,Lokugamage KG,Vu MN,Bopp N,Crocquet-Valdes PA,Kalveram B,Schindewolf C,Liu Y,Scharton D,Plante JA,Xie X,Aguilar P,Weaver SC,Shi PY,Walker DH,Routh AL,Plante KS,Menachery VD
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Journal
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PLoS pathogens
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Journal Info
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2022 Jun 21;18(6):e1010627
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Abstract
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While SARS-CoV-2 continues to adapt for human infection and transmission, genetic variation outside of the spike gene remains largely unexplored. This study investigates a highly variable region at residues 203-205 in the SARS-CoV-2 nucleocapsid protein. Recreating a mutation found in the alpha and omicron variants in an early pandemic (WA-1) background, we find that the R203K+G204R mutation is sufficient to enhance replication, fitness, and pathogenesis of SARS-CoV-2. The R203K+G204R mutant corresponds with increased viral RNA and protein both in vitro and in vivo. Importantly, the R203K+G204R mutation increases nucleocapsid phosphorylation and confers resistance to inhibition of the GSK-3 kinase, providing a molecular basis for increased virus replication. Notably, analogous alanine substitutions at positions 203+204 also increase SARS-CoV-2 replication and augment phosphorylation, suggesting that infection is enhanced through ablation of the ancestral 'RG' motif. Overall, these results demonstrate that variant mutations outside spike are key components in SARS-CoV-2's continued adaptation to human infection.
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Sequence Data
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-
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