Abstract：
The human cytomegalovirus (HCMV) UL24 and UL43 are tegument proteins that have recently been shown to interact with each other in a yeast two-hybrid system. By their overexpression in MRC5 cells, we demonstrate that these viral proteins interact with several important host proteins, especially Dicer and trans-activation response RNA binding protein. As these hots proteins are involved in regulating the production of cellular micro-RNAs, the cytomegalovirus (CMV) proteins could interfere with their actions to favor viral replication directly or through an immune escape mechanism. Double knockout of UL24 and UL43 does not show a remarkable effect on CMV entry or replication, but it significantly downregulates the expression of CMV-encoded miR-UL59, which is thought to regulate the expression of a downstream target UL16 binding protein 1 (ULBP1). Interestingly, the double knockout increases the expression of the ULBP1 recognized by the NKG2D activating receptor of natural killer cells. This study investigates the potential role of several proteins encoded by HCMV in regulating the host cellular environment to favor escape from immunity, and it also provides some basis for the future development of RNA-targeted small molecules to control HCMV infection.
摘要：
人巨细胞病毒（HCMV）UL24和UL43是被膜蛋白，最近已被证明在酵母双杂交系统中彼此相互作用。通过它们在MRC5细胞中的过度表达，我们证明了这些病毒蛋白与几种重要的宿主蛋白相互作用，特别是Dicer和反式激活应答RNA结合蛋白。由于这些hots蛋白参与调节细胞微小RNA的产生，巨细胞病毒(CMV)蛋白可以直接或通过免疫逃逸机制干扰其有利于病毒复制的作用.UL24和UL43的双重敲除对CMV进入或复制没有显着影响，但它显著下调CMV编码的miR-UL59的表达,这被认为是调节下游靶UL16结合蛋白1(ULBP1)的表达.有趣的是,双敲除增加自然杀伤细胞的NKG2D激活受体识别的ULBP1的表达。这项研究调查了HCMV编码的几种蛋白质在调节宿主细胞环境以促进逃避免疫中的潜在作用。为今后开发RNA靶向小分子控制HCMV感染提供了一定的依据。
