RRC ID 81459
Author Minato E, Kobayashi A, Aoshima K, Fukushi H, Kimura T.
Title Susceptibility of rat immortalized neuronal cell line Rn33B expressing equine major histocompatibility class 1 to equine herpesvirus-1 infection is differentiation dependent.
Journal Microbiol Immunol
Abstract Equine herpesvirus-1 (EHV-1), which causes encephalomyelitis in horses, shows endotheliotropism in the central nervous system of horses, and generally does not infect neurons. However, little is known about the mechanism underlying the resistance of neuron to EHV-1, due to the lack of convenient cell culture systems. In this study, we examined EHV-1 infection in immortalized Rn33B rat neuronal cells, which differentiate into neurons when cultured under nonpermissive conditions. Because murine cell lines are resistant to EHV-1 infections due to the lack of functional entry receptors for EHV-1, we used an Rn33B-derived cell line that stably expresses the equine MHC class 1 molecule, which acts as EHV-1 entry receptor (Rn33B-A68B2M cells). EHV-1 infected undifferentiated Rn33B-A68B2M 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-1 produced infectious viral progeny. While EHV-1 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-stimulated genes, were not activated regardless of whether cells were differentiated or not. These results suggest that neuronal differentiation of RN33B-A68B2M cells reduced their susceptibility to EHV-1, which is not due to different IFN responses. This culture system may be useful as an in vitro model for studying neuron-specific resistance to EHV-1, by investigating viral and host factors responsible for the difference in susceptibility between differentiated and undifferentiated cells.
Volume 64(2)
Pages 123-132
Published 2020-2-1
DOI 10.1111/1348-0421.12761
PMID 31758567
MeSH Animals Cell Differentiation Cell Line Encephalomyelitis / veterinary* Encephalomyelitis / virology Herpesviridae Infections* Herpesvirus 1, Equid / pathogenicity* Histocompatibility Antigens Class I / metabolism* Horse Diseases / virology Horses Immediate-Early Proteins / metabolism Interferons / metabolism Mice Neurons / metabolism Neurons / virology* Rats Virus Internalization
Resource
DNA material CSII-CMV-MCS-IRES2-Bsd (RDB04385) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394)