Yu Shu Pin, Ong Kien Chai, Tan Soon Hao, Ishikawa Tomohiro, Perera David, Hooi Yuan Teng, Wong Kum Thong
Department of Pathology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.
Department of Biomedical Science, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.
J Gen Virol. 2025 Sep;106(9). doi: 10.1099/jgv.0.002137.
The Japanese encephalitis virus (JEV), a leading cause of viral encephalitis, exists as similar but non-identical biological clones whose genomic variations/mutations may determine neurovirulence. Two biological clones purified from a brain-derived, clinical isolate were tested for neurovirulence using human neuronal cells (SK-N-MC) and mouse neuronal cells (NIE-115) and on a footpad-inoculation mouse model. One clone (JEV-M) demonstrated significantly reduced infectivity in both neuronal cells and the mouse model compared to another clone (JEV-V). Of the 2 gene point mutations in JEV-M, only the T175C mutation, which translates as an E protein residue 59, amino acid tyrosine to histidine change (Y59H), was found to be the neurovirulence determinant as confirmed by testing with infectious clones with or without these mutations. These novel findings could further our understanding of JEV neuropathogenesis and may be useful for future vaccine development.
日本脑炎病毒（JEV）是病毒性脑炎的主要病因，以相似但不完全相同的生物学克隆形式存在，其基因组变异/突变可能决定神经毒力。从脑源性临床分离株中纯化出的两个生物学克隆，使用人神经细胞（SK-N-MC）和小鼠神经细胞（NIE-115）以及足垫接种小鼠模型进行神经毒力测试。与另一个克隆（JEV-V）相比，一个克隆（JEV-M）在神经细胞和小鼠模型中的感染性均显著降低。在JEV-M的2个基因点突变中，只有T175C突变（该突变导致E蛋白第59位残基由氨基酸酪氨酸变为组氨酸（Y59H））被发现是神经毒力决定因素，这通过对有或无这些突变的感染性克隆进行测试得到了证实。这些新发现可能会加深我们对JEV神经发病机制的理解，并可能对未来的疫苗开发有用。
