EB病毒编码的脱氧尿苷三磷酸酶诱导免疫失调：对EB病毒相关疾病病理生理学的影响。

EBV-encoded dUTPase induces immune dysregulation: Implications for the pathophysiology of EBV-associated disease.

作者信息

Glaser Ronald, Litsky Monica L, Padgett David A, Baiocchi Robert A, Yang Eric V, Chen Min, Yeh Peir-En, Green-Church Kari B, Caligiuri Michael A, Williams Marshall V

机构信息

Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center, 333 W. 10th Avenue, Columbus, OH 43210, USA.

出版信息

Virology. 2006 Mar 1;346(1):205-18. doi: 10.1016/j.virol.2005.10.034.

DOI:10.1016/j.virol.2005.10.034

PMID:16321417

Abstract

Epstein-Barr virus (EBV) encodes for several enzymes that are involved in viral DNA replication. There is evidence that some viral proteins, by themselves, can induce immune dysregulation that may contribute to the pathophysiology of the virus infection. In this study, we focused on 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-1beta, 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.

摘要

爱泼斯坦-巴尔病毒（EBV）编码多种参与病毒DNA复制的酶。有证据表明，一些病毒蛋白自身可诱导免疫失调，这可能与病毒感染的病理生理学有关。在本研究中，我们聚焦于EBV编码的脱氧尿苷三磷酸核苷酸水解酶（dUTPase），并首次提供证据表明，dUTPase能够在体外诱导免疫失调，这表现为抑制刺激的外周血单个核细胞（PBMC）的复制，以及上调经纯化的EBV编码dUTPase处理的未刺激PBMC产生的几种促炎细胞因子，包括肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-8、白细胞介素-6和白细胞介素-10。CD14阳性细胞（单核细胞）的耗竭消除了EBV dUTPase处理诱导的细胞因子谱。这些数据支持这样一种假说，即EBV早期抗原复合物的至少一种蛋白可诱导免疫失调，并可能参与EBV相关疾病的病理生理学过程。