Vol 11: Type-I interferon response affects an inoculation dose-independent mortality in mice following Japanese encephalitis virus infection.Reportar como inadecuado



 Vol 11: Type-I interferon response affects an inoculation dose-independent mortality in mice following Japanese encephalitis virus infection.


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This article is from Virology Journal, volume 11.AbstractBackground: The laboratory mouse model is commonly employed to study the pathogenesis of encephalitic flaviviruses such as Japanese encephalitis virus JEV. However, it is known that some strains of these viruses do not elicit a typical mortality dose response curve from this organism after peripheral infection and the reason for it has not yet been fully understood. It is suggested that induction of more vigorous Type-I IFN IFN-I response might control early virus dissemination following increasing infectious challenge doses of the virus. Thus, the objective of this study was to examine this suggested role of IFN-I in the mortality of mice infected with various doses of JEV. Methods: Inbred 129 mice and their IFNAR KO A129 mice were subcutaneously inoculated with 100, 102, 104 or 106 pfu of JaOArS982 strain of JEV. Mice were weighed daily and observed for clinical signs. Virus titers in the brains and spleens of JEV-infected mice were determined by plaque forming assays. The upregulated mRNA levels of genes related to IFN-I response of mice were examined by real-time PCR. Results: The mortality rates of 129 mice infected with JaOArS982 did not significantly increase despite the increase in inoculation dose and no significant difference of viral loads was observed between their brains. However, there was clear elevation of the mRNA levels of interferon regulatory factor IRF3, IRF7, IRF9, MDA5 and RIG-I at 24 hours post-infection depending on the inoculation dose. In A129 mice, length of survival days and the viral loads of spleen and brain were observed to be inoculation dose-dependent. Conclusions: From these results, it is suggested that early IFN-I response elicited by high inoculation doses of JEV provides an anti-viral effect during the early phase of infection. Accordingly, virus replication is counteracted by IFN-I response at each increasing inoculation dose resulting in the interference of impending severe disease course or fatal outcome; hence, this might explain the inoculation dose-independent mortality in mice caused by Japanese encephalitis virus.



Autor: Aoki, Kotaro; Shimada, Satoshi; Simantini, Dash Sima; Tun, Mya Myat Ngwe; Buerano, Corazon C; Morita, Kouichi; Hayasaka, Daisuke

Fuente: https://archive.org/







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