CHIKV Mutation Detail Information

Virus Mutation CHIKV Mutation Q301R


Basic Characteristics of Mutations
Mutation Site Q301R
Mutation Site Sentence PP5 and PP6 contained the nsP4-C483Y mutation, but rather than nsP2-K704N they contained either an nsP3-Q301R or nsP3-N75K mutation.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region nsP3
Standardized Encoding Gene nsP3
Genotype/Subtype -
Viral Reference -
Functional Impact and Mechanisms
Disease Chikungunya Fever    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 39804924
Title Mutations in chikungunya virus nsP4 decrease viral fitness and sensitivity to the broad-spectrum antiviral 4'-Fluorouridine
Author Yin P,Sobolik EB,May NA,Wang S,Fayed A,Vyshenska D,Drobish AM,Parks MG,Lello LS,Merits A,Morrison TE,Greninger AL,Kielian M
Journal PLoS pathogens
Journal Info 2025 Jan 13;21(1):e1012859
Abstract Chikungunya virus (CHIKV) is an arthritogenic alphavirus that has re-emerged to cause large outbreaks of human infections worldwide. There are currently no approved antivirals for treatment of CHIKV infection. Recently, we reported that the ribonucleoside analog 4'-fluorouridine (4'-FlU) is a highly potent inhibitor of CHIKV replication, and targets the viral nsP4 RNA dependent RNA polymerase. In mouse models, oral therapy with 4'-FlU diminished viral tissue burdens and virus-induced disease signs. To provide critical evidence for the potential of 4'-FlU as a CHIKV antiviral, here we selected for CHIKV variants with decreased 4'-FlU sensitivity, identifying two pairs of mutations in nsP2 and nsP4. The nsP4 mutations Q192L and C483Y were predominantly responsible for reduced sensitivity. These variants were still inhibited by higher concentrations of 4'-FlU, and the mutations did not change nsP4 fidelity or provide a virus fitness advantage in vitro or in vivo. Pathogenesis studies in mice showed that the nsP4-C483Y variant caused similar disease and viral tissue burden as WT CHIKV, while the nsP4-Q192L variant was strongly attenuated. Together these results support the potential of 4'-FlU to be an important antiviral against CHIKV.
Sequence Data PRJNA1141983
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.