Kliche S, Kremmer E, Hammerschmidt W, Koszinowski U, Haas J
Max-von-Pettenkofer Institut, Genzentrum, Universität München, 81377 Munich, GSF Forschungszentrum, 80377 Munich, Germany.
J Virol. 1998 Oct;72(10):8143-9. doi: 10.1128/JVI.72.10.8143-8149.1998.
In patients with Kaposi's sarcoma (KS), human herpesvirus 8 (HHV-8) can invariably be detected in KS tumor tissue and, at a lower frequency, in prostate tissue and peripheral blood B lymphocytes. Whereas the majority of KS spindle cells are latently infected by HHV-8, linear HHV-8 genomes characteristic for lytic infection are found predominantly in the peripheral blood cells of KS patients. In this study, we show that HHV-8 can stably infect B lymphocytes in vitro in the presence of Epstein-Barr virus (EBV). We were able to generate immortalized HHV-8(+)/EBV+ lymphoblastoid cell lines (LCLs) derived from peripheral blood mononuclear cells (PBMC) of EBV- and EBV+ donors. In HHV-8(+)/EBV+ LCLs, which have the phenotype of activated B lymphocytes (CD19(+), surface immunoglobulin M, CD23(+), CD30(+), CD80(+)), HHV-8 was still present after more than 25 passages (more than 9 months of culture). Latent viral transcripts and proteins were present in nonstimulated HHV-8(+)/EBV+ LCLs. After induction by phorbol ester and n-butyrate, HHV-8(+)/EBV+ LCLs expressed lytic HHV-8 transcripts and proteins. Moreover, HHV-8 could be serially passaged from HHV-8(+)/EBV+ LCLs to fresh PBMC.
在卡波西肉瘤（KS）患者中，在KS肿瘤组织中总能检测到人类疱疹病毒8型（HHV-8），而在前列腺组织和外周血B淋巴细胞中检测到的频率较低。虽然大多数KS梭形细胞被HHV-8潜伏感染，但裂解感染特有的线性HHV-8基因组主要存在于KS患者的外周血细胞中。在本研究中，我们表明HHV-8在爱泼斯坦-巴尔病毒（EBV）存在的情况下能够在体外稳定感染B淋巴细胞。我们能够从EBV阴性和EBV阳性供体的外周血单个核细胞（PBMC）中生成永生化的HHV-8（+）/EBV+淋巴母细胞系（LCL）。在具有活化B淋巴细胞表型（CD19（+）、表面免疫球蛋白M、CD23（+）、CD30（+）、CD80（+））的HHV-8（+）/EBV+ LCL中，经过超过25代（超过9个月的培养）后HHV-8仍然存在。潜伏性病毒转录本和蛋白存在于未刺激的HHV-8（+）/EBV+ LCL中。经佛波酯和丁酸盐诱导后，HHV-8（+）/EBV+ LCL表达裂解性HHV-8转录本和蛋白。此外，HHV-8可以从HHV-8（+）/EBV+ LCL连续传代至新鲜的PBMC。
