Expression of human cytomegalovirus immune evasion genes

Human cytomegalovirus (HCMV) has several gene products, which are important for escape from immune surveillance. The viral US3 and US6 gene products are expressed at immediate-early and early times after infection, respectively. These viral gene products downregulate the surface expression of HLA class I molecules. There are two regulatory regions between the US3 and the US6 transcription units. The first region is a NF-κB responsive enhancer that promotes the immediate-early expression of the US3 gene and is designated the R2 enhancer. Upstream of the R2 enhancer is a region designated the R1 element that in transient transfection assays behaves as a silencer. Our hypothesis is that the R1 element binds specific host cellular proteins that regulate expression of the US3 and US6 genes. We determined that the R1 element in the context of the viral genome is not a silencer. In contrast, the expression of the US3 gene at 6 h after infection and the US6 gene at 24 h was higher when the R1 element was present. Therefore, the R1 element is a positive regulator of gene expression in the context of the viral genome in the infected cell. Human cell nuclear proteins bind to the R1 element and to related sequences from the Drosophila scs' boundary element. Two different affinity purified rabbit anti-Drosophila boundary element associated factor antibodies inhibited the binding of the human cell nuclear proteins to the HCMV R1 element. The identity of these R1-binding proteins and their importance for R1-function remains to be determined.