|
Basic Characteristics of Mutations
|
|
Mutation Site
|
S235F |
|
Mutation Site Sentence
|
Interestingly, the mobilities of the alpha variant bands were decreased compared to the KR mt indicating an even higher level of phosphorylation, potentially due to the alpha variant's additional nucleocapsid mutations at D3L and S235F. |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
N |
|
Standardized Encoding Gene
|
N
|
|
Genotype/Subtype
|
- |
|
Viral Reference
|
MN985325.1;MN996532.2;MT121216.1;AY278741.1;KF367457.1
|
|
Functional Impact and Mechanisms
|
|
Disease
|
-
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
- |
|
Location
|
America |
|
Literature Information
|
|
PMID
|
35728038
|
|
Title
|
Nucleocapsid mutations in SARS-CoV-2 augment replication and pathogenesis
|
|
Author
|
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
|
|
Journal
|
PLoS pathogens
|
|
Journal Info
|
2022 Jun 21;18(6):e1010627
|
|
Abstract
|
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.
|
|
Sequence Data
|
-
|
|
|