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Characterisation of a Japanese Encephalitis virus genotype 4 isolate from the 2022 Australian outbreak
Wilson Nguyen1, Narayan Gyawali1, Romal Stewart1
1QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4029, Australia.
Npj Viruses
|April 28, 2025
Summary
A new Japanese encephalitis virus (JEV) genotype 4 strain (JEVNSW/22) is less virulent in mice but infects human brain organoids. Existing JEV vaccines may offer protection, but neutralizing antibody responses are suboptimal.
Area of Science:
- Virology
- Neuroscience
- Immunology
Background:
- Japanese encephalitis virus (JEV) causes viral encephalitis.
- A novel JEV genotype 4 strain (JEVNSW/22) emerged in Australia.
- Understanding JEVNSW/22 pathogenicity and vaccine efficacy is crucial.
Purpose of the Study:
- Characterize JEVNSW/22 in mouse models and human brain organoids.
- Assess JEVNSW/22 virulence compared to other JEV genotypes.
- Evaluate neutralization of JEVNSW/22 by human sera from IMOJEV vaccination.
Main Methods:
- Infection studies in C57BL/6J, Irf7-/-, and Ifnar-/- mice.
- Infection of human cortical brain organoids (hBOs).
- Analysis of viral load, neuropathology, and antibody neutralization.
Main Results:
- JEVNSW/22 was less virulent than JEV genotypes 2 and 3 in mice.
- Irf7-/- mice provide a model for lethal neuroinvasive JEVNSW/22 infection.
- JEVNSW/22 showed robust infection in hBOs, though less than other strains.
- IMOJEV vaccination induced cross-neutralizing antibodies against JEVNSW/22, but with reduced titers.
Conclusions:
- Established JEVNSW/22 mouse and hBO models for infection studies.
- JEV vaccination may provide partial protection against this new genotype 4 strain.
- Further research is needed to optimize JEV vaccines against emerging strains.
