NS1’ protein expression in the JaOArS982 strain of Japanese encephalitis virus does not enhance virulence in mice

ABSTRACT

Using a mouse model,we previously demonstrated that subcutaneous infection with the JaTH160 strainof Japaneseencephalitis virus (JEV) causes significantly higher virulence and strongervirus propagation in the brain compared with that of the JaOArS982strain. We also showed that the JaTH160 strain,but not JaOArS982, expresses the NS1’ protein and that NS1’ enhances JEVproduction in avian cells and embryonated chicken eggs. In this study, weexamined whether NS1’ expression affects virulence in mice infected with theJaOArS982 and JaTH160 strains using the corresponding recombinant viruses S982-ICand JaTH-IC.Expression of the NS1’ protein in S982-IC diminishedthe mortality in mice, whereas S982-IC viruses without NS1’ caused 40% mortality.However, the viral loads in the brains of these mice were not significantlydifferent despite the difference in NS1’ expression. JaTH-IC viruses depletedof the NS1’ protein exhibited high mortality levels, similar to those of thevirus expressing NS1’.Previousstudies showed that the NS1’ protein plays a role in the enhanced virulenceof the JEV SA14 strain in mice. However, ourcurrent data suggest that NS1’ protein expression in S982-IC reduces,rather than enhances, the mortality in mice. Thus, the effect of NS1’ on pathogenicity <i>invivo</i> may vary among virus strains. Our data also suggest that the reducedmortality resulting from NS1’ expression in S982-IC is not simply due to viralreplication in the brains. Furtherinvestigation is needed to uncover the mechanism by which NS1’ affectspathogenicity in JEV-infected animals.