Suppression of the interferon-mediated innate immune response by pseudorabies virus
Suppression of the interferon-mediated innate immune response by pseudorabies virus
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DOI：
10.1128/jvi.00554-06
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发表时间：
2006-07-01
影响因子：
5.4
通讯作者：
Enquist, L. W.
中科院分区：
文献类型：
--
作者：
Brukman, Alla;Enquist, L. W.
伪狂犬病毒（PRV）是一种与人类病原体单纯疱疹病毒1型（HSV-1）和水痘带状疱疹病毒相关的甲型疱疹病毒。PRV能够感染和杀死多种哺乳动物。它是如何在如此多的宿主中避免先天免疫防御的尚不清楚。虽然已经研究了HSV-1的抗干扰素（IFN）策略，但对于PRV如何逃避IFN介导的免疫反应知之甚少。在这项研究中，我们确定野生型PRV感染是否可以克服在原代大鼠成纤维细胞中建立干扰素（IFN β）诱导的抗病毒状态。利用微阵列技术，我们发现当细胞同时感染野生型PRV菌株时，通常由ifn - β诱导的基因子集在这些细胞中没有被诱导表达。与主要组织相容性复合体I类抗原呈递和NK细胞活化相关的转录本表达减少，而与炎症相关的转录本要么不受影响，要么被病毒感染诱导。IFN刺激的基因表达受到抑制是因为IFN信号转导，特别是STAT1的磷酸化，在prv感染的细胞中变得不那么有效。至少有一种病毒粒子相关蛋白参与抑制STAT1酪氨酸磷酸化。这种解除ifn - β反应的能力，解释了为何毒力强的PRV感染对非自然宿主具有一致的致命性。
D Pseudorabies virus (PRV) is an alphaherpesvirus related to the human pathogens herpes simplex virus type 1 (HSV-1) and varicella-zoster virus. PRV is capable of infecting and killing a wide variety of mammals. How it avoids innate immune defenses in so many hosts is not understood. While the anti-interferon (IFN) strategies of HSV-1 have been studied, little is known about how PRV evades the IFN-mediated immune response. In this study, we determined if wild-type PRV infection can overcome the establishment of a beta interferon (IFN beta)-induced antiviral state in primary rat fibroblasts. Using microarray technology, we found that the expression of a subset of genes normally induced by IFN-beta in these cells was not induced when the cells were simultaneously infected with a wild-type PRV strain. Expression of transcripts associated with major histocompatibility complex class I antigen presentation and NK cell activation was reduced, while transcripts associated with inflammation either were unaffected or were induced by viral infection. This suppression of IFN-stimulated gene expression occurred because IFN signal transduction, in particular the phosphorylation of STAT1, became less effective in PRV-infected cells. At least one virion-associated protein is involved in inhibition of STAT1 tyrosine phosphorylation. This ability to disarm the IFN-beta response offers an explanation for the uniform lethality of virulent PRV infection of nonnatural hosts.