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However, little is known about the mechanism underlying the resistance of neuron to EHV\u20101, due to the lack of convenient cell culture systems. In this study, we examined EHV\u20101 infection in immortalized Rn33B rat neuronal cells, which differentiate into neurons when cultured under nonpermissive conditions. Because murine cell lines are resistant to EHV\u20101 infections due to the lack of functional entry receptors for EHV\u20101, we used an Rn33B\u2010derived cell line that stably expresses the equine MHC class 1 molecule, which acts as EHV\u20101 entry receptor (Rn33B\u2010A68B2M cells). EHV\u20101 infected undifferentiated Rn33B\u2010A68B2M cells more efficiently than differentiated cells, resulting in the production of progeny virus in the former but not in the latter. By contrast, both differentiated and undifferentiated cells infected with herpes simplex virus\u20101 produced infectious viral progeny. While EHV\u20101 infection induced stronger expression of IFN alpha gene in differentiated cells than in undifferentiated cells, downstream IFN responses, including phosphorylation of STAT1 (signal transducer and activator of transcription 1) and expression of IFN\u2010stimulated genes, were not activated regardless of whether cells were differentiated or not. These results suggest that neuronal differentiation of RN33B\u2010A68B2M cells reduced their susceptibility to EHV\u20101, which is not due to different IFN responses. This culture system may be useful as an <jats:italic>in vitro<\/jats:italic> model for studying neuron\u2010specific resistance to EHV\u20101, by investigating viral and host factors responsible for the difference in susceptibility between differentiated and undifferentiated cells.<\/jats:p>","DOI":"10.1111\/1348-0421.12761","type":"journal-article","created":{"date-parts":[[2019,11,23]],"date-time":"2019-11-23T08:54:41Z","timestamp":1574499281000},"page":"123-132","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Susceptibility of rat immortalized neuronal cell line Rn33B expressing equine major histocompatibility class 1 to equine herpesvirus\u20101 infection is differentiation dependent"],"prefix":"10.1111","volume":"64","author":[{"given":"Erina","family":"Minato","sequence":"first","affiliation":[{"name":"Laboratory of Comparative Pathology, Faculty of Veterinary Medicine Hokkaido University, Sapporo Hokkaido 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