Laboratory of Veterinary Epizootiology, Department of Veterinary Medicine, Nihon University, Kameino 1866, Fujisawa, Kanagawa, 252-0880, Japan.
Laboratory of Veterinary Microbiology, Department of Veterinary Medicine, Nihon University, Kameino 1866, Fujisawa, Kanagawa, 252-0880, Japan.
Virus Res. 2019 Aug;269:197641. doi: 10.1016/j.virusres.2019.197641. Epub 2019 Jun 19.
Bovine leukemia virus (BLV) causes enzootic bovine leukosis (EBL). The BLV genome encodes Tax protein, a transcriptional activator of viral gene expression that binds to the BLV long terminal repeat (LTR). Heat shock factor 1 (HSF1) is a known regulator of the heat shock response proteins, including heat shock proteins. In the present study, the BLV LTR was investigated for interaction of heat shock element (HSE) with HSF1 and the viral Tax protein. It could be confirmed that a functional HSE is well conserved in different BLV strains. The LTR transcriptional activity, as measured by luciferase reporter assay, was upregulated by bovine HSF1 - without Tax expression - in feline CC81 cells. The HSF1 activated LTR transcription by binding to the HSE. LTR-activation was lost upon HSE removal from the LTR and upon expression of a mutant HSF1 lacking the DNA-binding domain. We conclude that BLV LTR is activated to a basal level by host transcriptional factor HSF1, but without Tax protein involvement.
牛白血病病毒 (BLV) 引起地方性牛白血病 (EBL)。BLV 基因组编码 Tax 蛋白,它是病毒基因表达的转录激活因子,与 BLV 长末端重复序列 (LTR) 结合。热休克因子 1 (HSF1) 是热休克反应蛋白的已知调节剂,包括热休克蛋白。在本研究中,研究了 BLV LTR 与热休克元件 (HSE) 与 HSF1 和病毒 Tax 蛋白的相互作用。可以证实,不同 BLV 株中都很好地保守了功能性 HSE。通过荧光素酶报告基因测定,在猫 CC81 细胞中,牛 HSF1 在没有 Tax 表达的情况下,上调了 LTR 的转录活性。HSF1 通过与 HSE 结合激活 LTR 转录。从 LTR 中去除 HSE 以及表达缺乏 DNA 结合域的突变 HSF1 后,LTR 激活丧失。我们得出结论,BLV LTR 被宿主转录因子 HSF1 激活到基础水平,但不涉及 Tax 蛋白。