Lee Gyu Cheol, Yi Hyun Ah, Lee Chan Hee
Division of Life Sciences, College of Natural Sciences, and Biotechnology Research Institute, Chungbuk National University, 12 Gaeshindong, Cheongju, Chungbuk 361-763, South Korea.
Virus Res. 2006 May;117(2):209-14. doi: 10.1016/j.virusres.2005.08.018. Epub 2006 Mar 20.
Infection of human foreskin fibroblast (HFF) cells with human cytomegalovirus (HCMV) induces the secretion of soluble factors including interferon (IFN)-beta that stimulates human leukocyte antigen (HLA) class I expression. In this study, the mechanism of IFN-beta induction by HCMV was investigated. In HCMV-infected HFF cells, IFN-beta secretion increased at 6h post infection (h.p.i.). Reverse transcription polymerase chain reaction (RT-PCR) analysis using ultra violet (UV)-inactivated HCMV indicated that viral gene expression is not necessary for the stimulation of IFN-beta. Stimulation of IFN-beta by HCMV infection was not blocked by cycloheximide, an inhibitor of protein synthesis, further suggesting that the expression of HCMV genes is not required for the stimulation of IFN-beta gene transcription. IFN-beta may be produced from virus-infected cells as an inflammatory response and nuclear factor kappa B (NF-kappaB) plays a central role in inflammatory response. HCMV failed to induce the IFN-beta expression, when the virus-infected cells were treated with pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-kappaB, or LY294002 and wortmannin, inhibitors of phosphatidylinositol 3-kinase (PI3-K). The result suggests that PI3-K and/or NF-kappaB may be related with the induction pathway of IFN-beta by HCMV.
人巨细胞病毒（HCMV）感染人包皮成纤维细胞（HFF）可诱导包括干扰素（IFN）-β在内的可溶性因子分泌，而干扰素-β可刺激人类白细胞抗原（HLA）I类表达。在本研究中，对HCMV诱导IFN-β的机制进行了研究。在HCMV感染的HFF细胞中，感染后6小时（h.p.i.）IFN-β分泌增加。使用紫外线（UV）灭活的HCMV进行逆转录聚合酶链反应（RT-PCR）分析表明，病毒基因表达对于IFN-β的刺激并非必需。HCMV感染对IFN-β的刺激不受蛋白质合成抑制剂环己酰亚胺的阻断，这进一步表明IFN-β基因转录的刺激不需要HCMV基因的表达。IFN-β可能作为一种炎症反应从病毒感染的细胞中产生，而核因子κB（NF-κB）在炎症反应中起核心作用。当用NF-κB抑制剂吡咯烷二硫代氨基甲酸盐（PDTC）或磷脂酰肌醇3-激酶（PI3-K）抑制剂LY294002和渥曼青霉素处理病毒感染的细胞时，HCMV未能诱导IFN-β表达。结果表明，PI3-K和/或NF-κB可能与HCMV诱导IFN-β的途径有关。
