Neutralizing Antibody Induction and Cytotoxic T Lymphocyte Response to Nakayama-NIH and Beijing-1 as Japanese Encephalitis Virus Vaccine Strains

The Japanese encephalitis virus (JEV), a member of the Flaviviridae family and Flavivirus genus, is transmitted by mosquitoes. JEV, of which some 35,000 cases are recorded every year, is a positive RNA virus. Two types of JEV vaccines have been developed to prevent the onset of encephalitis in humans, namely formalin-inactivated and liveattenuated vaccines. JEV inactivated vaccines are usually made using the Nakayama-NIH or Beijing-1 strains of the JEV virus. In this study, the immunological response to the Nakayama-NIH and Beijing-1 strains was analyzed as part of the effort to compile basic data which could lead to the selection of a suitable vaccine strain. To this end, the virus titer of Beijing-1 was found to be two-fold higher than that of Nakayama-NIH by plaque assay. Moreover, Beijing-1-induced neutralizing antibodies showed a higher level of titers when confronted by Korean JEV isolates than Nakayama-NIH-induced neutralizing antibodies (1:320 vs. 1:160, respectively). However, as a minimum ratio of 1:10 neutralizing antibody titers are required to protect against JEV infection, both strains in effect exhibited a sufficient level of neutralizing antibody titers. What's more, Beijing-1 was found to induce a somewhat higher cytotoxic T lymphocyte (CTL) response than Nakayama-NIH. Taken together, this can be taken to mean that Beijing-1 may in fact be a more effective vaccine candidate strain when it comes to inducing a high level of protective immunity against JEV infection.

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.