Expression of viral and human dUTPase in Epstein-Barr virus-associated diseases
Expression of viral and human dUTPase in Epstein-Barr virus-associated diseases
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DOI：
10.1002/jmv.10234
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发表时间：
2002-12-01
影响因子：
12.7
通讯作者：
Niedobitek, G
中科院分区：
文献类型：
--
作者：
Fleischmann, J;Kremmer, E;Niedobitek, G
脱氧尿苷三磷酸酶（dUTR）催化dUTP水解为dUMP和焦磷酸盐，从而阻止尿嘧啶掺入复制DNA。先前对几种病毒模型的研究表明，病毒dUTPases可能是静息细胞中病毒复制所需的，而在增殖细胞中，细胞dUTPases可能取代突变病毒蛋白。使用单克隆抗体和免疫组化，EB病毒相关的非肿瘤性和肿瘤性疾病的病毒和人类dUTPases的表达进行了研究。口腔毛状白斑病是一种与艾滋病相关的舌部病变，已知支持EBV在上上皮细胞层中复制。与此一致，强的局灶性表达的EBV dUTR检测到口腔毛状白斑的上皮细胞层的上部，而表达的人dUTR仅限于基底增殖细胞室。此外，在传染性单核细胞增多症扁桃体中，罕见的散在小淋巴细胞表达EBV dUTR，与其他EBV裂解周期抗原的表达模式一致。这些发现与EBV在静息细胞中复制的概念一致。三种EBV相关肿瘤，霍奇金淋巴瘤，伯基特淋巴瘤和鼻咽癌，缺乏可检测的EBV dUTR表达，与EBV感染在这些肿瘤中主要是潜伏的概念一致。相比之下，在这些肿瘤中定期观察到人dUTR的表达。这些结果表明，EB病毒dUTPase可能是抗病毒治疗的合适靶点，并且人类dUTPase抑制剂应被证明可用于治疗人类肿瘤，包括EB病毒相关癌症。(C)2002 Wiley-Liss，Inc.
Deoxyuridine triphosphatase (dUTPase) catalyses the hydrolysis of dUTP to dUMP and pyrophosphate thus preventing the incorporation of uracil into replicating DNA. Previous studies of several virus models have suggested that viral dUTPases may be required for virus replication in resting cells whereas in proliferating cells cellular dUTPase may substitute for a mutant viral protein. Using monoclonal antibodies and immunohistochemistry, Epstein-Barr virus-associated nonneoplastic and neoplastic diseases were studied for the expression of viral and human dUTPases. Oral hairy leukoplakia, an AIDS-associated lesion of the tongue, is known to support EBV replication in the upper epithelial cell layers. In agreement with this, strong focal expression of EBV dUTPase was detected in the upper epithelial cell layers of oral hairy leukoplakia whereas expression of human dUTPase was confined to the basal proliferative cell compartment. Furthermore, in infectious mononucleosis tonsils, rare scattered small lymphoid cells expressed EBV dUTPase, consistent with the expression pattern of other EBV lytic cycle antigens. These findings are in agreement with the notion that EBV replicates in resting cells. Three EBV-associated tumours, Hodgkin lymphoma, Burkitt lymphoma and nasopharyngeal carcinoma, lacked detectable expression of EBV dUTPase, in agreement with the notion that EBV infection is largely latent in these tumours. By contrast, expression of human dUTPase was observed regularly in these tumours. These results suggest that EBV dUTPase may be a suitable target for anti-viral therapy and that inhibitors of human dUTPase should prove useful for the treatment of human tumours, including EBV-associated cancers. (C) 2002 Wiley-Liss, Inc.