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

Virology Journal

Daisuke Hayasaka¹  Kouichi Morita¹  Corazon C Buerano¹  Mya Myat Ngwe Tun¹  Dash Sima Simantini¹  Satoshi Shimada¹  Kotaro Aoki¹ 

[1] Department of Virology, Institute of Tropical Medicine, GCOE program, Leading Graduate School Program, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan

关键词: Inoculation dose-independent mortality;    Mouse model;    Type-I interferon;    Japanese encephalitis virus;   

Others  :  802819
DOI  :  10.1186/1743-422X-11-105

 received in 2014-01-29, accepted in 2014-05-21,  发布年份 2014

【 摘 要 】

Background

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 (IRF)3, 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.

【 授权许可】

   
2014 Aoki et al.; licensee BioMed Central Ltd.

【 图 表 】

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