UL5 and HCMV Pathogenesis: Investigating UL5’s Role in Lytic Replication and Latency

Human Cytomegalovirus (HCMV) is a common beta-Herpesvirus with a seroprevalence of approximately 60- 90\% among the general population. It remains a significant pathogen due to its latent, lifelong infection, and significant complications in those pregnant or immunosuppressed. To understand how this virus causes disease and persists, we are studying the function of a viral gene, UL5, with unknown function. To begin, we are determining the role of HCMV UL5 during lytic replication, a specific viral lifecycle stage where the virus is active and directly producing new virus particles. A prior proteomics study indicated that UL5 may interact directly with cellular proteins ANKRD13A and ST3Gal1. Both cellular proteins are important for protein regulation and immune function, which are key pathways dysregulated by HCMV. We determined that HCMV infection upregulates ANRKD13A and ST3GAL1. Subsequently we transfected cells with plasmid constructs containing UL5 to study its expression and cellular interactions individually. We found that ANKRD13A and ST3Gal1 were downregulated in UL5- transfected cells. We continue to explore the direct interaction of UL5 with ANKRD13A and ST3GAL1 at the protein level. Finally, we have preliminary data suggesting that UL5 is expressed during latency, another critical part of the lifecycle of HCMV. Our future studies will continue to characterize the role of HCMV UL5 in lytic and latent HCMV infection to advance our understanding of HCMV infection and latency and open avenues for targeted therapeutic interventions.