Susceptibility of rat immortalized neuronal cell line Rn33B expressing equine major histocompatibility class 1 to equine herpesvirus‐1 infection is differentiation dependent

Susceptibility of rat immortalized neuronal cell line Rn33B expressing equine major histocompatibility class 1 to equine herpesvirus‐1 infection is differentiation dependent
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表达马主要组织相容性 1 类的大鼠永生神经元细胞系 Rn33B 对马疱疹病毒 1 感染的敏感性是分化依赖性的

DOI:
10.1111/1348-0421.12761
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发表时间:
2020
影响因子:
2.6
通讯作者:
Kimura Takashi
Kimura Takashi
中科院分区:
医学4区
文献类型:
--
作者:
Minato Erina;Kobayashi Atsushi;Aoshima Keisuke;Fukushi Hideto;Kimura Takashi

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引起马脑脊髓炎的马疱疹病毒-1(EHV-1)在马的中枢神经系统中显示嗜内皮性,并且通常不感染神经元。然而,由于缺乏方便的细胞培养系统,对神经元对EHV-1的抵抗机制知之甚少。在这项研究中,我们研究了永生化Rn 33 B大鼠神经元细胞中的EHV-1感染,这些细胞在非允许条件下培养时分化为神经元。由于鼠细胞系由于缺乏EHV-1的功能性进入受体而对EHV-1感染具有抗性,因此我们使用了稳定表达马MHC 1类分子的Rn 33 B衍生细胞系,该分子作为EHV-1进入受体(Rn 33 B-A68 B2 M细胞)。EHV-1感染未分化的Rn 33 B-A68 B2 M细胞比分化的细胞更有效,导致前者产生子代病毒,而后者则没有。相比之下,用单纯疱疹病毒-1感染的分化和未分化细胞都产生感染性病毒后代。虽然EHV-1感染诱导分化细胞中IFN α基因的表达强于未分化细胞,但下游IFN应答,包括STAT 1(信号转导和转录激活因子1)的磷酸化和IFN刺激基因的表达,无论细胞是否分化,都不会被激活。这些结果表明RN 33 B-A68 B2 M细胞的神经元分化降低了它们对EHV-1的易感性,这不是由于不同的IFN应答。该培养系统可作为研究神经元对EHV-1特异性抗性的体外模型,通过研究导致分化和未分化细胞之间易感性差异的病毒和宿主因素。
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 anin vitromodel 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.
DOI: 10.3109/13550289909015812
发表时间: 1999-06-01
影响因子: 3.2
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Danaher, RJ;Jacob, RJ;Miller, CS
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DOI: 10.1111/j.1439-0450.1987.tb00418.x
发表时间: 1987
期刊: Zentralblatt fur Veterinarmedizin. Reihe B. Journal of veterinary medicine. Series B
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发表时间: 1999-02-16
影响因子: 11.1
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DOI: --
发表时间: 1983
影响因子: 3.3
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DOI: --
发表时间: 2006
期刊: Archives of Virology 151
影响因子: --
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