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Antigenic comparison of envelope protein E between Japanese encephalitis virus and some other flaviviruses using
Abstract:
The antigenic relationships between Japanese encephalitis (JE) virus and several other flaviviruses have been investigated using anti-JE virus monoclonal antibodies (MAbs). Seventeen MAbs directed against envelope protein E of JE virus were characterized and divided into eight MAb groups based on reactivity patterns in haemagglutination inhibition test, neutralization (N) test, ELISA and competitive binding assay with JE virus. The results suggest the existence of at least eight epitopes on the E protein of JE viruses. Analysis of cross-reactivity of the antibodies with several other flaviviruses indicated these findings JE virus, belonging to West Nile (WN) subgroup, is antigenically closely related to viruses in the same subgroup, i.e. Murray Valley encephalitis (MVE), WN and St. Louis encephalitis (SLE) viruses. Of these three viruses, JE virus has the closest relationship with MVE virus. WN virus is relatively close to JE virus, whereas SLE virus is the least closely related. Dengue viruses types 1 and 2, which belong to another subgroup of flaviviruses, show markedly less antigenic homology to JE virus. One of the critical N sites on the E protein showed JE virus specificity. Some cross-reactive antibodies which did not neutralize JE virus showed low but significant N activity against several other flaviviruses. Mixtures of several MAbs, which showed different reactivity patterns, potentiated the N activity against not only JE virus but also other members of the WN subgroup of flaviviruses, namely MVE, WN and SLE viruses.
Insights
Japanese encephalitis (JE) virus is closely related to Murray Valley encephalitis (MVE) and West Nile (WN) viruses, sharing antigenic sites on its envelope protein E. Monoclonal antibodies reveal distinct epitopes and cross-reactivity patterns within flaviviruses.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Japanese encephalitis (JE) virus is a significant human pathogen within the Flaviviridae family.
- Understanding the antigenic relationships among flaviviruses is crucial for vaccine development and diagnostics.
- The envelope protein E is a key target for neutralizing antibodies and determining viral relatedness.
Purpose of the Study:
- To investigate the antigenic relationships between JE virus and other flaviviruses.
- To characterize epitopes on the JE virus envelope protein E using monoclonal antibodies (MAbs).
- To assess the cross-reactivity of anti-JE virus MAbs with other flaviviruses.
Main Methods:
- Production and characterization of 17 MAbs against JE virus envelope protein E.
- Haemagglutination inhibition, neutralization (N) tests, ELISA, and competitive binding assays were employed.
- Cross-reactivity analysis was performed using various flaviviruses, including MVE, WN, SLE, and Dengue viruses.
Main Results:
- At least eight distinct epitopes were identified on the JE virus E protein.
- JE virus showed close antigenic relationships with MVE, WN, and SLE viruses (West Nile subgroup).
- JE virus demonstrated the closest antigenic relationship with MVE virus, followed by WN, and then SLE virus. Dengue viruses showed less homology.
Conclusions:
- JE virus is antigenically closely related to viruses in the West Nile subgroup, particularly MVE virus.
- Specific epitopes on the JE virus E protein contribute to its distinct antigenic profile.
- Combinations of MAbs with different reactivity patterns enhanced neutralization of JE virus and related flaviviruses.