Abstract

Japanese Encephalitis Virus (JEV) is responsible for over 30,000 annual cases of encephalitis worldwide, causing 30% mortality. JEV is thus a continuing threat to public health, so development of new antiviral drugs against JEV is desirable. Here, we examined JEV replication in mouse and used a short hairpin RNA JRi as the antiviral agent. The features of virus replication in neuron and survival rates of mice infected with JEV were different between virus strains. The mice infected with the virulent JEV strain (JaGAr01) were injected with pJRi (100 μg/mouse) which produced shRNAJRi. The survival rates of mice treated at 3 days before, the same day and 3 days after JEV infection were 22%, 78% and 44%, respectively. In addition, we demonstrated that the injection of pJRi induced interferon (IFN) production in cells and mice. These results suggest that the replication of JEV can be efficiently inhibited by RNAi and innate immunity including IFN. These data mean that pJRi has the inhibitory activity against JEV infection in vivo, and could be used as an antiviral drug to treat JEV infection.

Highlights

  • Japanese Encephalitis Virus (JEV) is a member of the flavivirus and small (40 - 60 nm) enveloped virus familyHow to cite this paper: Murakami, M., Tasaki, T., Nukuzuma, S., Minato, H., Nojima, T., Ishigaki, Y. and Takegami, T. (2016) Japanese Encephalitis Virus Replication and Inhibitory Effect of short hairpin RNAs (shRNAs) in Mice

  • In Japan, it is important to monitor the distribution of JEV, there have been less than 10 JE cases each year since 1992 [4]

  • We report that the difference in virulence between JEV strains and the antiviral activity of the JRishRNA in mice, and show its effect on interferon (IFN) production in vivo

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Summary

Introduction

Japanese Encephalitis Virus (JEV) is a member of the flavivirus and small (40 - 60 nm) enveloped virus familyHow to cite this paper: Murakami, M., Tasaki, T., Nukuzuma, S., Minato, H., Nojima, T., Ishigaki, Y. and Takegami, T. (2016) Japanese Encephalitis Virus Replication and Inhibitory Effect of shRNA in Mice. Japanese Encephalitis Virus (JEV) is a member of the flavivirus and small (40 - 60 nm) enveloped virus family. The genomic RNA, which contains a cap structure at the 5’-end and a specific tertiary structure at the 3’-end, encodes a single polyprote which is processed into three structural and seven nonstructural proteins. The viral structural proteins are encoded by the 5’-third of the Open Reading Frame (ORF), and consist of the capsid (C), membrane (M; formed by proteolytic cleavage of its precursor protein prM) and envelope (E) proteins. The nonstructural proteins (NS1 to NS5) are encoded by the remaining 3’ region of the ORF. The ORF is flanked by 5’- and 3’-untranslated regions (UTR), which were approximately 95 and 582 nt long, respectively [5]

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