Wonderling R S, Kyöstiö S R, Walker S L, Owens R A
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Virology. 1997 Sep 15;236(1):167-76. doi: 10.1006/viro.1997.8724.
The Rep68 and Rep78 proteins of adeno-associated virus type-2 (AAV) are multifunctional DNA binding proteins which are involved in the positive and negative regulation of AAV genes, as well as various cellular and heterologous viral genes. In this study we report that Rep68 enhances expression from the major immediate early promoter (MIEP) of human cytomegalovirus (HCMV). This Rep-mediated enhancement of RNA levels is abrogated by the introduction of a Rep recognition sequence (RRS) at either position -18 or -244 in the HCMV-MIEP. However, a mutant RRS (mRRS), which is not bound by Rep68 is unable to negate the effect of Rep68. Sequence analysis and electrophoretic mobility shift assays showed no Rep68 binding sites within the wild-type HCMV-MIEP. Rep68 may therefore be enhancing expression from the HCMV-MIEP by interacting with other regulatory proteins that have an effect on the expression from this promoter or by altering the expression of a cellular gene whose product influences the HCMV-MIEP. Our results may also help to explain the previous observation that coinfection with AAV enhances the cytopathic effect of HCMV.
2型腺相关病毒（AAV）的Rep68和Rep78蛋白是多功能DNA结合蛋白，参与AAV基因的正负调控，以及各种细胞和异源病毒基因的调控。在本研究中，我们报道Rep68增强了人巨细胞病毒（HCMV）主要立即早期启动子（MIEP）的表达。在HCMV-MIEP中-18或-244位置引入Rep识别序列（RRS）可消除这种Rep介导的RNA水平增强。然而，一个不被Rep68结合的突变RRS（mRRS）无法消除Rep68的作用。序列分析和电泳迁移率变动分析表明，野生型HCMV-MIEP内不存在Rep68结合位点。因此，Rep68可能通过与其他对该启动子表达有影响的调节蛋白相互作用，或通过改变一种细胞基因的表达来增强HCMV-MIEP的表达，该细胞基因的产物会影响HCMV-MIEP。我们的结果也可能有助于解释先前的观察结果，即AAV与HCMV共感染会增强HCMV的细胞病变效应。
