Meaghan Hancock, University of Guelph

Nicole L Diggins1, Luke Slind1, Jennifer Mitchell1, Yan Chen1, Devin Fachko1, Andrew H Pham1, Rebekah L Turner1, Patrizia Caposio1, Rebecca L. Skalsky1 and Meaghan H Hancock2 1Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR, USA 2Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON, Canada

Suppressing & Conquering

Successful latent infection of CD34 hematopoietic progenitor cells (HPCs) by human cytomegalovirus (HCMV) requires careful control of cell homeostasis. HPC proliferation and differentiation stimulates viral gene expression and replication, and thus precise control of these processes is necessary to maintain the viral genome in a latent state. Virally encoded miRNAs represent powerful tools used by HCMV to manipulate cell signaling pathways that are involved in latency establishment, maintenance, and reactivation. While previous work determined that HCMV stimulates beta-catenin-mediated Wnt signaling during reactivation in CD34 HPCs, here we show using biochemical and cell biology techniques as well as viral mutants and small molecule inhibitors that two HCMV miRNAs, miR-US5-2 and miR-US25-2, target the Wnt pathway adaptor protein Dvl3 specifically during latent infection. These results highlight how HCMV can regulate the same cell signaling pathway in opposing manners to regulate different stages of the virus lifecycle.