Identification of Japanese encephalitis virus-inducible genes in mouse brain and characterization of GARG39/IFIT2 as a microtubule-associated protein

Abstract

Several mouse central nervous system genes have been identified that are differentially regulated during Japanese encephalitis virus (JEV) infection, including those which have not been reported to be induced by any other neurotropic virus. Interestingly, ~80 % of JEV-inducible genes identified in this study are also induced by Sindbis virus, indicating activation of common host signalling pathways by these two viruses, despite their diverse life cycles. One of these, the glucocorticoid attenuated response gene 39 (GARG39, also known as IFIT2, ISG54 and MuP54) was characterized further. It was demonstrated that GARG39 protein interacts with microtubules in vitro, co-localizes with β-tubulin in vivo and is enriched in the mitotic spindle of non-neuronal cells undergoing mitosis. While GARG39 was known for a long time as an inflammation-inducible glucocorticoid attenuated protein, its identification as a microtubule-associated protein in this study suggests a possible role for this protein in cell proliferation, virion assembly/transport and microtubule dynamics.