Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
Retrovirology. 2013 Nov 12;10:132. doi: 10.1186/1742-4690-10-132.
Emerging evidence suggests that human cytomegalovirus (HCMV) is highly prevalent in tumours of different origin. This virus is implied to have oncogenic and oncomodulatory functions, through its ability to control host gene expression. Human endogenous retroviruses (HERV) are also frequently active in tumours of different origin, and are supposed to contribute as cofactors to cancer development. Due to the high prevalence of HCMV in several different tumours, and its ability to control host cell gene expression, we sought to define whether HCMV may affect HERV transcription.
Infection of 3 established cancer cell lines, 2 primary glioblastoma cells, endothelial cells from 3 donors and monocytes from 4 donors with HCMV (strains VR 1814 or TB40/F) induced reverse transcriptase (RT) activity in all cells tested, but the response varied between donors. Both, gammaretrovirus-related class I elements HERV-T, HERV-W, HERV-F and ERV-9, and betaretrovirus-related class II elements HML-2 - 4 and HML-7 - 8, as well as spuma-virus related class III elements of the HERV-L group were up-regulated in response to HCMV infection in GliNS1 cells. Up-regulation of HERV activity was more pronounced in cells harbouring active HCMV infection, but was also induced by UV-inactivated virus. The effect was only slightly affected by ganciclovir treatment and was not controlled by the IE72 or IE86 HCMV genes.
Within this brief report we show that HCMV infection induces HERV transcriptional activity in different cell types.
新出现的证据表明,人类巨细胞病毒(HCMV)在不同来源的肿瘤中高度普遍存在。该病毒通过控制宿主基因表达,具有致癌和致癌调节功能。人类内源性逆转录病毒(HERV)在不同来源的肿瘤中也经常活跃,并被认为是癌症发展的协同因子。由于 HCMV 在几种不同肿瘤中的高流行率及其控制宿主细胞基因表达的能力,我们试图确定 HCMV 是否会影响 HERV 转录。
用 HCMV(株 VR1814 或 TB40/F)感染 3 种已建立的癌细胞系、2 种原发性脑胶质瘤细胞、来自 3 个供体的内皮细胞和来自 4 个供体的单核细胞,在所有测试的细胞中均诱导逆转录酶(RT)活性,但反应在供体之间有所不同。γ逆转录病毒相关的 I 类元件 HERV-T、HERV-W、HERV-F 和 ERV-9,β逆转录病毒相关的 II 类元件 HML-2-4 和 HML-7-8,以及与 spuma 病毒相关的 HERV-L 组 III 类元件,均在 GliNS1 细胞中对 HCMV 感染产生反应而上调。HERV 活性的上调在具有活跃 HCMV 感染的细胞中更为明显,但也被紫外线灭活的病毒诱导。该效应仅受更昔洛韦处理的轻微影响,不受 HCMV IE72 或 IE86 基因的控制。
在本简短报告中,我们表明 HCMV 感染诱导不同细胞类型的 HERV 转录活性。