Apoptotic Neuronal Death in the Mouse Brain Induced by Experimental Japanese Encephalitis Virus Infection / 대한해부학회지

Japanese encephalitis virus (JEV)may cause acute encephalitis in humans and induce severe cytopathic effects in various types of cultured cells. To investigate whether JEV infection induces apoptosis, we examined DNA fragmentation and apoptosis in the specific region of the JEV infected mouse brain by DNA oligonucleosomal laddering and in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)technique and immunohistochemical study. JEV infections in the mouse brain were detected in the telencephalon, the diencephalons, and the brain stem, but not in the cerebellum and the hippocampus. Fragmentation of cellular DNA into oligonucleosome-length ladders was only observed in tissue samples prepared from the cerebral cortex. In addition, the large number of TUNEL-positive cells was observed in the cerebral cortex. Double-labeling experiment with TUNEL staining and immunostaining for the JEV showed that TUNEL-positive neurons containing JEV immunoreactivity. These results suggest that JEV infection may evoke apoptotic neuronal death in the mouse brain, which plays an important role in the pathogenesis of Japanese encephalitis.

In vivo Study on the Japanese Encephalitis: Viral Localization and Histopathology in the Mouse Brain / 대한해부학회지

Japanese encephalitis is a potentially lethal disease of the central nervous system caused by infection with Japanese encephalitis virus (JEV). JEV is the most common cause of encephalitis over a large part of eastern Asia. To establish and characterize in vivo model to study the Japanese encephalitis, the immunohistochemical localization of JEV and the histopathological finding were investigated in the brains of young adult mice infected with JEV by intraperitoneal inoculation. JEV was localized to neurons in discrete regions of the brain. Histopathological finding showed typical pattern of acute viral encephalitis, such as inflammatory cell infiltration in brain parenchyme and perivascular cuffs of mononuclear cells. These results suggest that this in vivo system can be used to study the mechanism of virus entry into the brain, cell specific tropism, and pathophysiology in Japanese encephalitis.

Analysis of the Three Dimensional Structure of Envelope Protein of the Japnes Encephalitis virus Isolated in Korea

Three dimensional structures of envelope protein from Korean isolates and Nakayama-NIH strain of Japanese encephalitis virus (JEV) were deduced by a computer program (HyperChem 4.0 Chemplus 1.0) based on the data of the three dimentional structure of Tick-borne encephalitis virus. In the three dimensional structure of envelope protein, neutralizing epitope and T-helper cell recognition site of C-terminal region of Korean isolates were structually similar to those of Nakayama-NIH but the N-terminal region was not. Korean JE isolates were compared with Nakayama-NIH strain by using cross-neutralization antibody test. Neutralizing activities of Korean isolates derived from guinea pigs were higher than those of Nakayama-NIH strain against Korean isolates, although the polyclonal antibody titers of Nakayama-NIH showed 1:160 to 1:640 against Korean isolates. According to the results from three dimentional structures and cross-neutralization analyses, the antigenic difference between Korean JE isolates and Nakayama-NIH strain may be dependent on structural difference of envelope protein.