A vhs-like activity of bovine herpesvirus-1

A vhs-like activity of bovine herpesvirus-1
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DOI:
10.1007/s007050070038
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发表时间:
2000-01-01
影响因子:
2.7
通讯作者:
Srikumaran, S
Srikumaran, S
中科院分区:
医学4区
文献类型:
--
作者:
Hinkley, S;Ambagala, APN;Srikumaran, S

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牛疱疹病毒1型(BHV-1)是牛的主要病原体,可引起动物免疫功能低下等严重疾病。在体外,BHV-1感染下调了主要组织相容性复合体(MHC)I类分子的表面表达,这对宿主适当的抗病毒免疫应答至关重要。北方印迹分析显示,MHC I类和II类分子的mRNA在BHV-1感染的细胞中显著下调,早在感染后2 h就开始下调。此外,两个管家基因肌动蛋白和甘油醛-6-磷酸脱氢酶(GAPDH)的mRNA表达也受到抑制后感染。BHV-1对细胞代谢的诱导作用类似于单纯疱疹病毒(HSV)的病毒体宿主关闭(vhs)活性。与HSV vhs活性相似,在放线菌素D(ActD)存在下感染的细胞中,推定的BHV-1 vhs活性未被消除,这表明vhs功能不需要病毒基因表达,推定的vhs蛋白与病毒粒子相关。序列比较表明BHV-1开放阅读框与HSV vhs序列具有60%的相似性。这个推定的BHV-1开放阅读框包含α疱疹病毒vhs蛋白的四个保守区域。由于HSV vhs突变体表现出较低的毒力和良好的免疫原性,我们认为BHV-1 vhs(-)突变体可能具有作为候选疫苗的潜力。
Bovine herpesvirus 1 (BHV-1) is a major pathogen of cattle, causing significant disease including immunosuppression in infected animals. In vitro, the surface expression of major histocompatibility complex (MHC) class I molecules, crucial for an appropriate anti-viral immune response of the host, is downregulated by BHV-1 infection. Northern blot analyses revealed that the mRNAs for MHC class I and class II molecules were significantly down-regulated in BHV-1 infected cells, starting as early as 2h after infection. Furthermore, mRNA expression of the two house keeping genes actin and glyceraldehyde-6-phosphate dehydrogenase (GAPDH) was also repressed after infection. This BHV-1 induced effect on cellular metabolism resembled the virion host shutoff (vhs) activity of herpes simplex virus (HSV). Similar to the HSV vhs activity, the putative BHV-1 vhs activity was not abrogated in cells infected in the presence of actinomycin D (ActD) which suggested that no viral gene expression is required for the vhs function and the putative vhs protein is associated with the virion. Sequence comparison indicated a BHV-1 open reading frame having a 60% similarity to the HSV vhs sequence. This putative BHV-1 open reading frame contained the four conserved regions of the alphaherpesvirus vhs protein. Since an HSV vhs-mutant exhibited less virulence and good immunogenicity, we suggest that a BHV-1 vhs(-) mutant may hold promising potential as a candidate vaccine.