Dupin N, Fisher C, Kellam P, Ariad S, Tulliez M, Franck N, van Marck E, Salmon D, Gorin I, Escande J P, Weiss R A, Alitalo K, Boshoff C
Departments of Oncology and Molecular Pathology, Royal Free and University College Medical School, UCL, London, United Kingdom W1P 6BT.
Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4546-51. doi: 10.1073/pnas.96.8.4546.
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 <10% of cells forming the walls of ectatic vessels. In nodular KS, HHV-8 is present in cells surrounding slit-like vessels and 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-1, 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.
人疱疹病毒8型（HHV - 8，也称为卡波西肉瘤相关疱疹病毒）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。尚未证实HHV - 8在早期KS中普遍存在。我们使用一种针对由ORF73编码的HHV - 8潜伏核抗原-1（LNA - 1）的单克隆抗体（LN53），来研究HHV - 8潜伏感染的细胞类型在斑片状、斑块状和结节状KS、MCD及PEL中的分布情况。在早期KS中，HHV - 8存在于形成扩张血管壁的细胞中，比例小于10%。在结节状KS中，HHV - 8存在于裂隙样血管周围的细胞以及超过90%的梭形细胞中，但不存在于正常血管内皮细胞中。此外，HHV - 8与血管内皮生长因子受体-3（VEGFR - 3）共定位，VEGFR - 3是淋巴管和前体内皮细胞的标志物。在早期KS病变中，VEGFR - 3的表达比LNA - 1更广泛，这表明HHV - 8并非直接诱导VEGFR - 3阳性内皮细胞的增殖。在MCD中，HHV - 8存在于套区大免疫母细胞性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见到LNA - 1染色，这支持了这些疾病与HHV - 8之间不存在任何病因学关联。
