Integration of human herpesvirus 6 in a Burkitt's lymphoma cell line
Integration of human herpesvirus 6 in a Burkitt's lymphoma cell line
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DOI：
10.1046/j.1365-2141.1998.00903.x
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发表时间：
1998-09-01
影响因子：
6.5
通讯作者：
Miyoshi, I
中科院分区：
文献类型：
--
作者：
Daibata, M;Taguchi, T;Miyoshi, I
人类疱疹病毒6型（HHV-6）基因组已在几种人类淋巴系统恶性肿瘤中发现，但HHV-6基因组的构型尚未得到很好的描述。我们建立了HHV-6阳性、EB病毒阴性的伯基特淋巴瘤细胞系Katata。本研究对Katata细胞中HHV-6基因组的状态进行了研究，Gardella凝胶分析未检测到线性和环状HHV-6 DNA。荧光原位杂交技术使我们能够在单细胞水平上直接观察整合的HHV-6 DNA。在中期染色体上只检测到一个病毒DNA整合位点，它优先位于22号染色体长臂（22 q13）。用12-O-十四烷酰基-佛波醇-13-乙酸酯（TPA）或钙离子载体A23187处理细胞，导致HHV-6立即早期基因和晚期基因的诱导，正丁酸钠也引起HHV-6基因的表达。TPA的诱导作用与A23187或正丁酸酯联合使用时协同增强。我们的研究首次提供了一个潜伏性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。
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.