HCV Mutation Detail Information

Virus Mutation HCV Mutation T2381A


Basic Characteristics of Mutations
Mutation Site T2381A
Mutation Site Sentence On the contrary, in genotype 6 k, the same epitope had a variant sequence of DAGSDAGSY with two amino acids changed at T2381A and A2382G, resulting in a differing CTL score of 0.82 (Table 1).
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region
Standardized Encoding Gene
Genotype/Subtype 6k
Viral Reference -
Functional Impact and Mechanisms
Disease HCV Infection    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 39881992
Title In silico analysis of the effect of HCV genotype-specific polymorphisms in Core, NS3, NS5A, and NS5B proteins on T-cell epitope processing and presentation
Author Baig S,Berikkara A,Khalid R,Subhan SA,Abbas T,Abidi SH
Journal Frontiers in microbiology
Journal Info 2025 Jan 15;15:1498069
Abstract BACKGROUND: HCV genotypes are 30-35% polymorphic at the nucleotide level, while subtypes within the same genotype differ by nearly 20%. Although previous studies have shown the immune escape potential of several mutations within the HCV proteins, little is known about the effect of genotype/subtype-specific gene polymorphism on T-cell immunity. Therefore, this study employed several in silico methods to examine the impact of genotype/subtype-specific polymorphisms in Core, NS3, NS5A, and NS5B sequences on T cell epitope processing and HLA-epitope interactions. METHODS: For this study, 8,942, 17,700, 14,645, and 3,277 HCV Core, NS3, NS5A, and NS5B sequences, respectively, from eight genotypes and 21 subtypes were retrieved from the Los Alamos HCV Database. Next, the NetCTL tool was employed to predict Cytotoxic T Lymphocyte (CTL) epitopes based on combined proteasomal cleavage, TAP efficacy, and HLA class I receptor binding scores. PEP-FOLD was used to model selected epitopes, followed by peptide-HLA docking using HPEPDOCK. Finally, molecular dynamics simulations were conducted for 200 ns using Desmond software to analyze differences in HLA-epitope (from different HCV genotypes) interaction kinetics and dynamics. RESULTS: A total of 3,410, 8,054, 6,532, and 14,015 CTL epitopes were observed in the HCV Core, NS3, NS5A, and NS5B sequences, respectively. Significant genotype/subtype-specific variations in CTL values and docking scores were observed among NS3, NS5A, and NS5B proteins. In silico results reveal that epitopes from genotype 6b (NS3), 6d/r (NS5B), 6o and 6 k (NS5A) exhibit higher immunogenicity than other genotypes, forming more energetically stable complexes with host receptors. These epitopes, compared to those from the same positions but different genotypes, showed binding energies of -144.24 kcal/mol, -85.30 kcal/mol, and - 43 kcal/mol, respectively. Over a 200 ns MD simulation, GT 6b and 6d/r epitopes displayed up to a 40% stronger binding energy with the HLA receptor. These findings suggest that patients infected with GT 6 may experience enhanced T cell responsiveness and broader immunogenicity. CONCLUSION: Our study suggests that genotype/subtype-specific polymorphism in HCV may result in altered immune responses by modulating T-cell epitope processing and interaction with HLA receptors. Further experimental studies can be performed to confirm the effect of genotype/subtype-specific polymorphisms on T cell-mediated immune response.
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.