What is the week point of flavivirus? : Biological role of viral protein NS4a and 3' UTR of genomic RNA

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Japanese encephalitis virus (JEV) is the important human pathogen and causes acute meningioencephalitis, resulting in fatality rate of ca 30%. The aim of this project is to clarify the biological function of nonstructural viral protein NS4a and 3' UTR of genomic RNA.(1) Here we used JEV-JaGAr01 strain and the cultured human-cell lines, KN73, HepG2, and IMR32. We constructed several NS4a-expression vectors and the luciferase reporter system containing JEV-3' UTR. The feature of NS4a expression in the cells was different between wild and mutant proteins. Luciferase activity was remarkably decreased in the presence of mutant sequence at the 3' end of RNA. The results suggest that the mutation of NS4a and 3' UTR influences the activity for viral protein synthesis in the cells.(2) In the viral pathogenesity, it is essential to clarify host gene expression induced by flavivirus infection. Here we used DNA microarray (Affymetrix) method to examine host gene expression in JEV-infected cells including acute and persistent infection. From the comparison of human liver derived cell line KN73 and neuroblastoma cell line IMR32, we confirmed the expression of interferon (IFN) related genes was critical to decide viral replication level. In addition, JEV-persistently infected cell lines (JK1) which has been established in our laboratory indicated relatively low expression of IFN-related genes in comparison with the acute infection. Taken together with the expression data of other host genes, the feature of JEV replication seems to be regulated by the expression of IFN, IFN related genes and other host genes.