Daibata M, Taguchi T, Taguchi H, Miyoshi I
Department of Medicine, Kochi Medical School, Japan.
Br J Haematol. 1998 Sep;102(5):1307-13. doi: 10.1046/j.1365-2141.1998.00903.x.
Human herpesvirus 6 (HHV-6) genome has been found in several human lymphoid malignancies, but configuration of the HHV-6 genome has not been well delineated. We established the HHV-6-positive, Epstein-Barr virus-negative Burkitt's lymphoma cell line Katata. In this study we investigated the status of the HHV-6 genome in Katata cells. Neither linear nor circular HHV-6 DNA was detected by Gardella gel analysis. The fluorescence in situ hybridization technique enabled us to directly visualize the integrated HHV-6 DNA at the single-cell level. Only one integrated site of viral DNA was detected in metaphase chromosomes and it was preferentially located at the long arm of chromosome 22 (22q13). Treatment of the cells with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or with calcium ionophore A23187 led to induction of the HHV-6 immediate-early gene as well as the late gene. Sodium n-butyrate also gave rise to expression of the HHV-6 genes. The TPA inducibility was synergistically enhanced when combined with A23187 or n-butyrate. Our study provides, for the first time, an in vitro model system of latent HHV-6 infection whose genome is integrated into host DNA of lymphoma cells.
人类疱疹病毒6型（HHV - 6）基因组已在多种人类淋巴恶性肿瘤中被发现，但HHV - 6基因组的结构尚未得到很好的描述。我们建立了HHV - 6阳性、爱泼斯坦 - 巴尔病毒阴性的伯基特淋巴瘤细胞系Katata。在本研究中，我们调查了Katata细胞中HHV - 6基因组的状态。通过Gardella凝胶分析未检测到线性或环状的HHV - 6 DNA。荧光原位杂交技术使我们能够在单细胞水平直接观察到整合的HHV - 6 DNA。在中期染色体中仅检测到一个病毒DNA的整合位点，且其优先位于22号染色体长臂（22q13）上。用12 - O - 十四酰佛波醇 - 13 - 乙酸酯（TPA）或钙离子载体A23187处理细胞可诱导HHV - 6立即早期基因以及晚期基因的表达。丁酸钠也能使HHV - 6基因表达。当与A23187或丁酸钠联合使用时，TPA的诱导能力会协同增强。我们的研究首次提供了一种潜伏性HHV - 6感染的体外模型系统，其基因组整合到淋巴瘤细胞的宿主DNA中。
