Distribution of human herpesvirus-8 latently infected cells in Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma
Distribution of human herpesvirus-8 latently infected cells in Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma
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DOI：
10.1073/pnas.96.8.4546
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发表时间：
1999-04-13
影响因子：
11.1
通讯作者：
Boshoff, C
中科院分区：
文献类型：
--
作者：
Dupin, N;Fisher, C;Boshoff, C
人类疱疹病毒8型（HHV-8，也称为KSHV）与卡波西肉瘤（KS）、多中心Castleman病（MCD）和原发性渗出性淋巴瘤（PEL）的发病机制有关。HHV-8在早期KS中的普遍存在尚未得到证实。我们用抗HHV-8潜伏核抗原-1（LNA-1）的单克隆抗体（LN 53）研究了HHV-8潜伏感染的细胞类型在斑片、斑块和结节KS、MCD和PEL中的分布。在早期KS中，HHV-8存在于90%的梭形细胞中，但不存在于正常血管内皮中。此外，HHV-8与血管内皮生长因子受体-3（VEGFR-3）共定位，血管内皮生长因子受体-3是淋巴管和前体内皮的标志物。在早期KS病变中，VEGFR-3比LNA-1表达更广泛，表明HHV-8不直接诱导VEGFR-3阳性内皮细胞增殖。在MCD中，HHV-8存在于套区大免疫母细胞B细胞中。在多发性骨髓瘤、前列腺癌和血管肉瘤的样本中未观察到LNA-1染色，支持这些疾病与HHV-8之间不存在任何病因学联系。
Human herpesvirus 8 (HHV-8, also called KSHV) is linked to the etiopathogenesis of Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL). The universal presence of HHV-8 in early KS has not yet been shown. We used a mAb (LN53) against latent nuclear antigen-1 (LNA-1) of HHV-8 encoded by ORF73 to study the distribution of the cell types latently infected by HHV-8 in patch, plaque, and nodular KS, MCD, and PEL. In early KS, HHV-8 is present in 90% of spindle cells, but not in normal vascular endothelium. In addition, HHV-8 colocalizes with vascular endothelial growth factor receptor-3 (VEGFR-3), a marker of lymphatic and precursor endothelium. In early KS lesions, VEGFR-3 is more extensively expressed than LNA-I, indicating that HHV-8 is not inducing the proliferation of VEGFR-3-positive endothelium directly. In MCD, HHV-8 is present in mantle zone large immunoblastic B cells. No staining for LNA-1 is seen in samples from multiple myeloma, prostate cancer, and angiosarcoma, supporting the absence of any etiological link between these diseases and HHV-8.