Human cytomegalovirus (HCMV) causes a variety of human diseases and has recently been associated with accelerated atherosclerosis and coronary restenosis following angioplasty. Latent infection of hematopoietic cells of the bone marrow and blood monocytes has been demonstrated while productive infection of a number of different types of differentiated cells has been shown. Our laboratory is interested in viral regulatory elements and the viral and cellular proteins that regulate latency and productive infection.
In specific aim 1 we propose to determine the role of specific regulatory motifs on viral gene expression in undifferentiated and differentiated cells relevant to HCMV latency and productive infection. Regulatory elements that repress transcription from the divergent major immediate early (undifferentiated cells) and UL127 (differentiated cells) promoters will be analyzed.
In aim 2 we will determine the functions of the HCMV IE2 gene and gene products that are relevant to the viral life cycle. Using recombinant replication defective adenovirus vectors that express IE72 or IE86 proteins and recombinant HCMV with IE1 and IE2 genes deleted, we will investigate the function of these viral gene products in the context of virus infection.
In specific aim 3, the function of the R1 and R2 elements which are positioned between the US3 and US6 gene families will be investigated. It is proposed that the R1 element insulates the R2 enhancer from effecting the US6 transcription unit. Together these aims will characterize HCMV regulatory elements and viral proteins that influence viral gene expression in undifferentiated and differentiated cells relevant to HCMV latency and productive infection.
