The ORF37 (UL24) is a neuropathogenicity determinant of equine herpesvirus 1 (EHV-1) in the mouse encephalitis model

The ORF37 (UL24) is a neuropathogenicity determinant of equine herpesvirus 1 (EHV-1) in the mouse encephalitis model
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DOI:
10.1016/j.virol.2010.02.012
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发表时间:
2010-05-10
期刊:
影响因子:
3.7
通讯作者:
Fukushi, Hideto
Fukushi, Hideto
中科院分区:
医学3区
文献类型:
--
作者:
Kasem, Samy;Yu, Mi Htay Htay;Fukushi, Hideto

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以马疱疹病毒1型(EquineHerpesvirus 1,EHV-1)神经致病株Ab 4p为基础,建立了EHV-1细菌人工染色体克隆(Ab 4pBAC)。用选择盒rpsL-neo基因替换编码UL 24的ORF 37,以产生ORF 37缺失突变体Ab 4p Delta ORF 37。用Ab 4p Delta ORF 37基因组DNA转染RK-13细胞产生感染性病毒,表明ORF 37对细胞培养物中EHV-1复制不是必需的。ORF 37的缺失对邻近基因ORF 36和ORF 38的转录表达以及MDBK细胞的生长活性没有影响。Ab 4p Delta ORF 37在CBA/N1小鼠中丧失神经致病性,如不存在任何神经病症和死亡所指示。Ab 4p Delta ORF 37在培养的神经细胞中的生长比亲本和回复突变体病毒低一个数量级。这些结果表明ORF 37是EHV-1在小鼠脑炎模型中的神经致病性决定因子。(C)2010年爱思唯尔公司All rights reserved.
Equine herpesvirus 1 (EHV-1) bacterial artificial chromosome clone (Ab4p BAC) was established based on neuropathogenic strain Ab4p. ORF37 encoding UL24 was replaced with a selection cassette, rpsL-neo gene, to produce an ORF37 deletion mutant, Ab4p Delta ORF37. Transfection of RK-13 cells with Ab4p Delta ORF37 genome DNA produced infectious virus, indicating that ORF37 is not essential for EHV-1 replication in cell culture. Deletion of ORF37 had no effect on the transcript expression of neighboring genes, ORF36 and ORF38, and the growth activity in MDBK cells. Ab4p Delta ORF37 lost neuropathogenicity in CBA/N1 mice as indicated by the absence of any neurological disorders and death. The growth of Ab4p Delta ORF37 in cultivated neural cells was one order of magnitude lower than that of parental and revertant viruses. These results indicated that the ORF37 is a neuropathogenicity determinant of EHV-1 in the mouse encephalitis model. (C) 2010 Elsevier Inc. All rights reserved.