UC San Diego

Human cytomegalovirus (HCMV) is of clinical importance and is the leading viral cause of birth defects. HCMV infections are also problematic for immunocompromised individuals and organ transplant recipients. This virus infects a variety of cell types in vivo, and although laboratory studies have demonstrated that HCMV does not productively infect embryonic stem cells, the main symptoms in newborns constitute defects in early nervous system development. While the HCMV life cycle has been studied extensively in human fibroblasts, our understanding is limited in terms of how different cell types in the host contribute to the overall infection. The HCMV genome not only has the capacity to encode hundreds of protein products, but also itself encodes microRNAs (miRNAs), and these viral miRNAs reach high abundance during the infection. Here, I first describe comprehensive deep-sequencing characterization of both viral and human miRNAs during lytic HCMV infection of primary fibroblasts. In addition to the identification of two new HCMV-encoded miRNAs, my results also include the finding that the genomic cluster of human miRNAs 182/96/183 is highly upregulated by late stages of infection. For the second stage of my HCMV studies, I present analysis of the full RNA transcriptomes of three different primary cell types undergoing infection. This work was initiated to compare infected neural progenitors with other more permissive cell types, namely fibroblasts and endothelial cells. In my comparative transcriptome analysis I uncovered a wealth of new findings related to conserved effects of HCMV infection on host RNA processing patterns. Finally, I report preliminary results from high-throughput chromosome conformation studies, which have suggested the existence of virus-host DNA interactions during HCMV infection