EBV-encoded dUTPase induces immune dysregulation: Implications for the pathophysiology of EBV-associated disease
EBV-encoded dUTPase induces immune dysregulation: Implications for the pathophysiology of EBV-associated disease
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DOI：
10.1016/j.virol.2005.10.034
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发表时间：
2006-03-01
期刊：
影响因子：
3.7
通讯作者：
Williams, MV
中科院分区：
文献类型：
--
作者：
Glaser, R;Litsky, ML;Williams, MV
EB病毒（EBV）编码参与病毒DNA复制的几种酶。有证据表明，一些病毒蛋白本身可诱导免疫失调，这可能有助于病毒感染的病理生理学。在这项研究中，我们重点关注EBV编码的脱氧尿苷三磷酸核苷酸水解酶（dUTR），并首次证明dUTR能够诱导体外免疫失调，如抑制刺激的外周血单核细胞（PBMC）的复制和上调几种促炎细胞因子，包括TNF-α，IL-1 β，IL-8，IL-6，和用纯化的EBV编码的dUTR处理的未刺激的PBMC产生的IL-10。CD 14阳性细胞（单核细胞）的消耗消除了EBV dUTR治疗诱导的细胞因子谱。这些数据支持以下假设：EBV早期抗原复合物中至少有一种蛋白可以诱导免疫失调，并可能参与EBV相关疾病的病理生理学。(c)2005年爱思唯尔公司All rights reserved.
Epstein-Barr virus (EBV) encodes for several enzymes that are involved in viral DNA replication. There is evidence that some viral proteins, by themselves, call induce immune dysregulation that may contribute to the pathophysiology of the virus infection. In this study, we focused oil the EBV-encoded deoxyuridine triphosphate nucleotidohydrolase (dUTPase) and present the first evidence that the dUTPase is able to induce immune dysregulation in vitro as demonstrated by the inhibition of the replication of stimulated peripheral blood mononuclear cells (PBMCs) and the upregulation of several proinflammatory cytokines including TNF-alpha, IL-1 beta, IL-8, IL-6, and IL-10 produced by unstimulated PBMCs treated with purified EBV-encoded dUTPase. Depletion of CD14-positive cells (monocytes) eliminated the cytokine profile induced by EBV dUTPase treatment. The data support the hypothesis that at least one protein of the EBV early antigen complex can induce immune dysregulation and may be involved in the pathophysiology of EBV-associated disease. (c) 2005 Elsevier Inc. All rights reserved.