{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T15:40:11Z","timestamp":1756741211268,"version":"3.44.0"},"reference-count":44,"publisher":"Microbiology Society","issue":"9","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004386","name":"Universiti Malaya","doi-asserted-by":"crossref","award":["UM.C\/625\/1\/HIR\/MOHE\/MED\/06"],"award-info":[{"award-number":["UM.C\/625\/1\/HIR\/MOHE\/MED\/06"]}],"id":[{"id":"10.13039\/501100004386","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004386","name":"Universiti Malaya","doi-asserted-by":"crossref","award":["PG285-2016A"],"award-info":[{"award-number":["PG285-2016A"]}],"id":[{"id":"10.13039\/501100004386","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:p>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 <jats:italic>in vitro<\/jats:italic> for neurovirulence using human neuronal cells (SK-N-MC) and mouse neuronal cells (NIE-115) and <jats:italic>in vivo<\/jats:italic> 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 <jats:italic>E<\/jats:italic> 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. 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