Japanese encephalitis virus (JEV) is a pathogen that causes severe vector-borne
zoonotic diseases, thereby posing a serious threat to human health. Although JEV is potentially neurotropic, its pathogenesis and distribution in the host have not been fully elucidated. In this study, an infected mouse model was established using a highly virulent P3 strain of JEV. Immunohistochemistry and in situ hybridization, combined with anatomical imaging of the mouse brain, were used to dynamically localize the virus and construct three-dimensional (3D) images. Consequently, onset of mild clinical signs occurred in some mice at 3.5 d post JEV
infection, while most mice displayed typical neurological signs at 6 d post-
infection (dpi). Moreover, brain pathology revealed typical changes associated with non-suppurative
encephalitis, which lasted up to 8 d. The earliest detection of
viral antigen was achieved at 3 dpi in the thalamus and medulla oblongata. At 6 dpi, the positive
viral antigen signals were mainly distributed in the cerebral cortex, olfactory area, basal ganglia, thalamus, and brainstem regions in mice. At 8 dpi, the
antigen signals gradually decreased, and the localization of JEV tended to concentrate in the cerebrum and thalamus, while no
viral antigen was detected in the brain at 21 dpi. In this model, the
viral antigen was first expressed in the reticular thalamic nucleus (Rt), and the virus content is relatively stable. The expression of the
viral antigen in the hippocampal CA2 region, the anterior olfactory nucleus, and the deep mesencephalic nucleus was high and persistent. The 3D images showed that viral signals were mostly concentrated in the parietal cortex, occipital lobe, and hippocampus, near the mid-sagittal plane. In the early stages of
infection in mice, a large number of
viral antigens were detected in denatured and necrotic neurons, suggesting that JEV directly causes neuronal damage. From the time of its entry, JEV is widely distributed in the central nervous system thereby causing extensive damage.