IV Mutation Detail Information

Virus Mutation IV Mutation N484A


Basic Characteristics of Mutations
Mutation Site N484A
Mutation Site Sentence Only H5 N484A HA2 stem mutant protein immunization increased the numbers of antibody-secreting cells, germinal center B cells, and memory B cells targeting the stem helix A epitopes in splenocytes.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region HA
Standardized Encoding Gene HA
Genotype/Subtype H1N1;H5N1
Viral Reference AFF60787;ACP41934
Functional Impact and Mechanisms
Disease -
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location Thailand;America
Literature Information
PMID 27440889
Title Unmasking Stem-Specific Neutralizing Epitopes by Abolishing N-Linked Glycosylation Sites of Influenza Virus Hemagglutinin Proteins for Vaccine Design
Author Liu WC,Jan JT,Huang YJ,Chen TH,Wu SC
Journal Journal of virology
Journal Info 2016 Sep 12;90(19):8496-508
Abstract Influenza virus hemagglutinin (HA) protein consists of two components, i.e., a globular head region and a stem region that are folded within six disulfide bonds, plus several N-linked glycans that produce a homotrimeric complex structure. While N-linked glycosylation sites on the globular head are variable among different strains and different subtypes, N-linked glycosylation sites in the stem region are mostly well conserved among various influenza virus strains. Targeting highly conserved HA stem regions has been proposed as a useful strategy for designing universal influenza vaccines. Since the HA stem region is constituted by an HA1 N-terminal part and a full HA2 part, we expressed a series of recombinant HA mutant proteins with deleted N-linked glycosylation sites in the HA1 stem and HA2 stem regions of H5N1 and pH1N1 viruses. Unmasking N-glycans in the HA2 stem region (H5 N484A and H1 N503A) was found to elicit more potent neutralizing antibody titers against homologous, heterologous, and heterosubtypic viruses. Unmasking the HA2 stem N-glycans of H5HA but not H1HA resulted in more CR6261-like and FI6v3-like antibodies and also correlated with the increase of cell fusion inhibition activity in antisera. Only H5 N484A HA2 stem mutant protein immunization increased the numbers of antibody-secreting cells, germinal center B cells, and memory B cells targeting the stem helix A epitopes in splenocytes. Unmasking the HA2 stem N-glycans of H5HA mutant proteins showed a significantly improvement in the protection against homologous virus challenges but did so to a less degree for the protection against heterosubtypic pH1N1 virus challenges. These results may provide useful information for designing more effective influenza vaccines. IMPORTANCE: N-linked glycosylation sites in the stem regions of influenza virus hemagglutinin (HA) proteins are mostly well conserved among various influenza virus strains. Targeting highly conserved HA stem regions has been proposed as a useful strategy for designing universal influenza vaccines. Our studies indicate that unmasking the HA2 stem N-glycans of recombinant HA proteins from H5N1 and pH1N1 viruses induced more potent neutralizing antibody titers against homologous and heterosubtypic viruses. However, only immunization with the H5N1 HA2 stem mutant protein can refocus B antibody responses to the helix A epitope for inducing more CR6261-like/FI6v3-like and fusion inhibition antibodies in antisera, resulting in a significant improvement for the protection against lethal H5N1 virus challenges. These results may provide useful information for designing more effective influenza vaccines.
Sequence Data -
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.