HEV Mutation Detail Information

Virus Mutation HEV Mutation T324S


Basic Characteristics of Mutations
Mutation Site T324S
Mutation Site Sentence To examine the influence of the identified ORF2 variants on the replication capacity of HEV, we introduced the different SNVs (P25S, G38S, A64T, G71R, P79S, S95P, V245I, and T324S) into the Kernow-C1/p6 strain (WT) (SI Appendix, Fig. S1A) and performed reverse-transcription quantitative polymerase chain reaction (RT qPCR) to quantify viral RNA and immunofluorescence staining to detect ORF2 protein.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region ORF2
Standardized Encoding Gene ORF2
Genotype/Subtype Genotype 3
Viral Reference JQ679013
Functional Impact and Mechanisms
Disease Chronic Hepatitis E     Cell line    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment Ribavirin
Location Germany
Literature Information
PMID 35969792
Title A ribavirin-induced ORF2 single-nucleotide variant produces defective hepatitis E virus particles with immune decoy function
Author Meister TL,Bruggemann Y,Nocke MK,Ulrich RG,Schuhenn J,Sutter K,Gomer A,Bader V,Winklhofer KF,Broering R,Verhoye L,Meuleman P,Vondran FWR,Camuzet C,Cocquerel L,Todt D,Steinmann E
Journal Proceedings of the National Academy of Sciences of the United States of America
Journal Info 2022 Aug 23;119(34):e2202653119
Abstract Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and is the leading cause of enterically transmitted viral hepatitis worldwide. Ribavirin (RBV) is currently the only treatment option for many patients; however, cases of treatment failures or posttreatment relapses have been frequently reported. RBV therapy was shown to be associated with an increase in HEV genome heterogeneity and the emergence of distinct HEV variants. In this study, we analyzed the impact of eight patient-derived open reading frame 2 (ORF2) single-nucleotide variants (SNVs), which occurred under RBV treatment, on the replication cycle and pathogenesis of HEV. The parental HEV strain and seven ORF2 variants showed comparable levels of RNA replication in human hepatoma cells and primary human hepatocytes. However, a P79S ORF2 variant demonstrated reduced RNA copy numbers released in the supernatant and an impairment in the production of infectious particles. Biophysical and biochemical characterization revealed that this SNV caused defective, smaller HEV particles with a loss of infectiousness. Furthermore, the P79S variant displayed an altered subcellular distribution of the ORF2 protein and was able to interfere with antibody-mediated neutralization of HEV in a competition assay. In conclusion, an SNV in the HEV ORF2 could be identified that resulted in altered virus particles that were noninfectious in vitro and in vivo, but could potentially serve as immune decoys. These findings provide insights in understanding the biology of circulating HEV variants and may guide development of personalized antiviral strategies in the future.
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.