IV Mutation Detail Information

Virus Mutation IV Mutation R430L


Basic Characteristics of Mutations
Mutation Site R430L
Mutation Site Sentence In addition, R430L, K432E or K435E in the 430-435 region was a common mutation in all resistant NA genes.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region NA
Standardized Encoding Gene NA
Genotype/Subtype -
Viral Reference t A/Puerto Rico/8/34 wild type
Functional Impact and Mechanisms
Disease Influenza A    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment oseltamivir;DS
Location Puerto Rico
Literature Information
PMID 25234090
Title Dextran sulfate-resistant A/Puerto Rico/8/34 influenza virus is associated with the emergence of specific mutations in the neuraminidase glycoprotein
Author Yamada H,Nagao C,Haredy AM,Mori Y,Mizuguchi K,Yamanishi K,Okamoto S
Journal Antiviral research
Journal Info 2014 Nov;111:69-77
Abstract Dextran sulfate (DS) is a negatively charged sulfated polysaccharide that suppresses the replication of influenza A viruses. The suppression was thought to be associated with inhibition of the hemagglutinin-dependent fusion activity. However, we previously showed that suppression by DS was observed not only at the initial stage of viral infection, but also later when virus is released from infected cells due to inhibition of neuraminidase (NA) activity. In the present study, we isolated DS-resistant A/Puerto Rico/8/34 (PR8) influenza viruses and analyzed the inhibition by DS. We found six mutations in NA genes of five independent resistant PR8 viruses and each resistant NA gene had two mutations. All mutations were from basic to acidic or neutral amino acids. In addition, R430L, K432E or K435E in the 430-435 region was a common mutation in all resistant NA genes. To determine which amino acid(s) are responsible for this resistance, a panel of recombinant viruses containing a PR8 and A/WSN/33(WSN) chimeric NA gene or an NA gene with different mutation(s) was generated using reverse genetics. Using recombinant viruses containing a PR8/WSN chimeric NA, we showed that one third of the C-terminal region of PR8 NA was responsible for DS-sensitivity. Recombinant viruses with a single mutation in NA replicated better than wild-type PR8 in the presence of DS, but were still DS-sensitive. However, replication of recombinant viruses with double mutations from the resistant viruses was not affected by the presence or absence of DS. In addition, resistant recombinant viruses were found to be sensitive to the NA inhibitor, oseltamivir and the oseltamivir-resistant recombinant virus was sensitive to DS. These results suggested that DS is an NA inhibitor with a different mechanism of action from the currently used NA inhibitors and that DS could be used in combination with these inhibitors to treat influenza virus infections.
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.