Human Merkel cell polyomavirus infection I. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors.

Human Merkel cell polyomavirus infection I. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors.
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DOI:
10.1002/ijc.24510
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发表时间:
2009-09-15
影响因子:
6.4
通讯作者:
Chang Y
Chang Y
中科院分区:
医学1区
文献类型:
--
作者:
Shuda M;Arora R;Kwun HJ;Feng H;Sarid R;Fernández-Figueras MT;Tolstov Y;Gjoerup O;Mansukhani MM;Swerdlow SH;Chaudhary PM;Kirkwood JM;Nalesnik MA;Kant JA;Weiss LM;Moore PS;Chang Y

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默克尔细胞多瘤病毒(MCV)是最近发现的一种人类病毒,与非洲绿猴嗜淋巴细胞多瘤病毒密切相关。 MCV DNA 整合在约 80% 的默克尔细胞癌 (MCC) 中,这是一种与慢性淋巴细胞白血病 (CLL) 等淋巴恶性肿瘤相关的神经内分泌皮肤癌。为了评估 MCV 感染及其与人类疾病的关系,我们开发了一种单克隆抗体,可以特异性识别内源性和转染的 MCV 大 T (LT) 抗原。我们显示 MCV LT 蛋白的表达定位于来自 MCC 的肿瘤细胞的细胞核,具有 PCR 定量的 MCV 基因组,每个细胞平均有 5.2 个(范围 0.8-14.3)个 T 抗原 DNA 拷贝。这种推定的病毒癌蛋白在肿瘤细胞中的表达为 MCV 导致 MCC 的一个亚型这一观点提供了机制基础。相比之下,尽管在接受调查的 325 例血液淋巴恶性肿瘤中,有 2.2% 也通过 DNA PCR 显示出 MCV 感染的证据,但在高病毒拷贝数下,没有一个呈阳性,并且在组织微阵列上检查的 173 例淋巴恶性肿瘤中,肿瘤细胞中没有一个表达 MCV LT 蛋白。与其他一些人类多瘤病毒一样,淋巴细胞可能作为 MCV 感染的组织储存库,但与 MCC 相关的血液淋巴恶性肿瘤不太可能由 MCV 引起。
Merkel cell polyomavirus (MCV) is a recently discovered human virus closely related to African green monkey lymphotropic polyomavirus. MCV DNA is integrated in ~80% of Merkel cell carcinomas (MCC), a neuroendocrine skin cancer linked to lymphoid malignancies such as chronic lymphocytic leukemia (CLL). To assess MCV infection and its association with human diseases, we developed a monoclonal antibody that specifically recognizes endogenous and transfected MCV large T (LT) antigen. We show expression of MCV LT protein localized to nuclei of tumor cells from MCC having PCR quantified MCV genome at an average of 5.2 (range 0.8–14.3) T antigen DNA copies per cell. Expression of this putative viral oncoprotein in tumor cells provides the mechanistic underpinning supporting the notion that MCV causes a subset of MCC. In contrast, although 2.2% of 325 hematolymphoid malignancies surveyed also showed evidence for MCV infection by DNA PCR, none were positive at high viral copy numbers, and none of 173 lymphoid malignancies examined on tissue microarrays expressed MCV LT protein in tumor cells. As with some of the other human polyomaviruses, lymphocytes may serve as a tissue reservoir for MCV infection, but hematolymphoid malignancies associated with MCC are unlikely to be caused by MCV.
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