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Basic Characteristics of Mutations
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Mutation Site
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E484A |
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Mutation Site Sentence
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We showed by ELISA that ACE2-competitive IGHV1-69 mAbs, LY-CoV555, MW01, and DH1043, are generally sensitive to E484 mutations (Omicron BA.1 has E484A) but the non-ACE2-competitive IGHV1-69 mAbs, R1-32 and FC08, are relatively insensitive to the E484 mutations (Figure 4(E)). |
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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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RBD |
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Standardized Encoding Gene
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S
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Genotype/Subtype
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Omicron(BA.1) |
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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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36288106
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Title
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Shared IGHV1-69-encoded neutralizing antibodies contribute to the emergence of L452R substitution in SARS-CoV-2 variants
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Author
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Yan Q,Hou R,Huang X,Zhang Y,He P,Zhang Y,Liu B,Wang Q,Rao H,Chen X,Zhao X,Niu X,Zhao J,Xiong X,Chen L
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Journal
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Emerging microbes & infections
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Journal Info
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2022 Dec;11(1):2749-2761
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Abstract
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SARS-CoV-2 variants continue to emerge facing established herd immunity. L452R, previously featured in the Delta variant, quickly emerged in Omicron subvariants, including BA.4/BA.5, implying a continued selection pressure on this residue. The underlying links between spike mutations and their selective pressures remain incompletely understood. Here, by analyzing 221 structurally characterized antibodies, we found that IGHV1-69-encoded antibodies preferentially contact L452 using germline-encoded hydrophobic residues at the tip of HCDR2 loop. Whereas somatic hypermutations or VDJ rearrangements are required to acquire L452-contacting hydrophobic residues for non-IGHV1-69 encoded antibodies. Antibody repertoire analysis revealed that IGHV1-69 L452-contacting antibody lineages are commonly induced among COVID-19 convalescents but non-IGHV1-69 encoded antibodies exhibit limited prevalence. In addition, we experimentally demonstrated that L452R renders most published IGHV1-69 antibodies ineffective. Furthermore, we found that IGHV1-69 L452-contacting antibodies are enriched in convalescents experienced Omicron BA.1 (without L452R) breakthrough infections but rarely found in Delta (with L452R) breakthrough infections. Taken together, these findings support that IGHV1-69 population antibodies contribute to selection pressure for L452 substitution. This study thus provides a better understanding of SARS-CoV-2 variant genesis and immune evasion.
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Sequence Data
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-
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