YFV Mutation Detail Information

Virus Mutation YFV Mutation A83E


Basic Characteristics of Mutations
Mutation Site A83E
Mutation Site Sentence We found the A83E mutation played a key role in reducing neutralizing sensitivity to YF-17D-vaccinated mouse sera.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region E
Standardized Encoding Gene envelope
Genotype/Subtype -
Viral Reference NC_002031;KF769016
Functional Impact and Mechanisms
Disease Cell line    
Immune Y
Target Gene IFNA1    CD4    CD8A   
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 40019254
Title A single residue in domain II of envelope protein of yellow fever virus is critical for neutralization sensitivity
Author Lou Y-N,Sun M-X,Li K,Xiong X-C,Zhou C,Cao T-S,Li X-F,Qin C-F
Journal Journal of virology
Journal Info 2025 Apr 15;99(4):e0177024
Abstract The live-attenuated yellow fever (YF) vaccine strain 17D (referred to as YF-17D) is the only commercially available vaccine against YF. Recent yellow fever virus (YFV) isolates of South American genotype I (SAI) showed reduced sensitivity to sera from individuals vaccinated with YF-17D. However, the underlying mechanisms remain inadequately elucidated. Here we conducted a screening of a panel of amino acid changes prevalent in domain II of the envelope protein (EDII) of SAI YFV isolates. Each mutation was introduced into the infectious clone of YF-17D utilizing standard reverse genetics. Subsequent neutralization assays demonstrated that the A83E mutant was more sensitive to sera from YF-17D-vaccinated mice and individuals than YF-17D did. Additionally, the A83E mutant displayed neurovirulence and viscerotropic characteristics comparable to those of the parental YF-17D in murine models. Notably, administration of a single dose of the A83E mutant resulted in an enhanced neutralization response against this variant compared to YF-17D and provided complete protection against lethal YFV challenge in mice. Collectively, these findings not only identify a crucial amino acid residue that influences the neutralization sensitivity of YFV but also provide a promising candidate for the development of an updated YF vaccine. IMPORTANCE: The YF-17D vaccine has been used to prevent YF disease. However, recent strains belonging to the SAI displayed reduced sensitivity to the antibodies produced by vaccination, raising concerns about potential future outbreaks. To identify potential amino acid residues responsible for the decreased neutralizing activity of YF-17D-vaccinated sera, we conducted a screening and generated recombinant viruses with amino acid changes specific to the SAI in EDII using the YF-17D genome as a genetic backbone. We found the A83E mutation played a key role in reducing neutralizing sensitivity to YF-17D-vaccinated mouse sera. Importantly, the A83E mutant maintained a comparable attenuation phenotype to YF-17D but elicited enhanced neutralization activity and conferred protection in mice. Together, we identify a key amino acid residue responsible for the neutralization escape of SAI YFV isolates. We propose that this substitution could act as a target for developing an updated YF-17D vaccine.
Sequence Data DQ235229;AY968065;KU921608;U54798;KY885000;KF907504
Mutation Information
Note
Basic Characteristics of Mutations
  • Mutation Site: The specific location in a gene or protein sequence where a change occurs.
  • Mutation Level: The level at which a mutation occurs, including the nucleotide or amino acid level.
  • Mutation Type: The nature of the mutation, such as missense mutation, nonsense mutation, synonymous mutation, etc.
  • Gene/Protein/Region: Refers to the specific region of the virus where the mutation occurs. Including viral genes, viral proteins, or a specific viral genome region. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main
  • Gene/Protein/Region studied in the article is marked.
  • Genotype/Subtype: Refers to the viral genotype or subtype where the mutation occurs. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main Genotype/Subtype studied in the article is marked.
  • Viral Reference: Refers to the standard virus strain used to compare and analyze viral sequences.
Functional Impact and Mechanisms
  • Disease: An abnormal physiological state with specific symptoms and signs caused by viral infection.
  • Immune: The article focuses on the study of mutations and immune.
  • Target Gene: Host genes that viral mutations may affect.
Clinical and Epidemiological Correlations
  • Clinical Information: The study is a clinical or epidemiological study and provides basic information about the population.
  • Treatment: The study mentioned a certain treatment method, such as drug resistance caused by mutations. If the study does not specifically indicate the relationship between mutations and their correspondence treatment, the main treatment studied in the article is marked.
  • Location: The source of the research data.
Literature Information
  • Sequence Data: The study provides the data accession number.