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Basic Characteristics of Mutations
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Mutation Site
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Q222A |
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Mutation Site Sentence
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In contrast to the previously observed interactions of NSP5 and NSP8 with TRIM7, a mutant of M lacking the degron signal (M-Q222A) interacted efficiently with TRIM7 (Fig. |
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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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M |
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Standardized Encoding Gene
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M
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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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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39616206
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Title
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TRIM7 ubiquitinates SARS-CoV-2 membrane protein to limit apoptosis and viral replication
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Author
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Gonzalez-Orozco M,Tseng HC,Hage A,Xia H,Behera P,Afreen K,Penaflor-Tellez Y,Giraldo MI,Huante M,Puebla-Clark L,van Tol S,Odle A,Crown M,Teruel N,Shelite TR,Moreno-Contreras J,Terasaki K,Makino S,Menachery V,Endsley M,Endsley JJ,Najmanovich RJ,Bashton M,Stephens R,Shi PY,Xie X,Freiberg AN,Rajsbaum R
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Journal
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Nature communications
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Journal Info
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2024 Nov 30;15(1):10438
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Abstract
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SARS-CoV-2 is a highly transmissible virus that causes COVID-19 disease. Mechanisms of viral pathogenesis include excessive inflammation and viral-induced cell death, resulting in tissue damage. Here we show that the host E3-ubiquitin ligase TRIM7 acts as an inhibitor of apoptosis and SARS-CoV-2 replication via ubiquitination of the viral membrane (M) protein. Trim7(-/-) mice exhibit increased pathology and virus titers associated with epithelial apoptosis and dysregulated immune responses. Mechanistically, TRIM7 ubiquitinates M on K14, which protects cells from cell death. Longitudinal SARS-CoV-2 sequence analysis from infected patients reveal that mutations on M-K14 appeared in circulating variants during the pandemic. The relevance of these mutations was tested in a mouse model. A recombinant M-K14/K15R virus shows reduced viral replication, consistent with the role of K15 in virus assembly, and increased levels of apoptosis associated with the loss of ubiquitination on K14. TRIM7 antiviral activity requires caspase-6 inhibition, linking apoptosis with viral replication and pathology.
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Sequence Data
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GSE268640
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