UL25 Deletion in hCMV and Impacts on Viral Replication Cycles

Abstract

Human Cytomegalovirus (hCMV) is a beta herpes virus that impacts a significant portion of the adult U.S. population (50‐94% seroprevalence, depending on the region). Furthermore, hCMV is the leading infectious cause of congenital defects, predominantly sensory neural hearing loss and various neurological disorders. hCMV is a problem for immunocompromised transplant recipients. A major challenge in dealing with hCMV infections, as well as herpes virus infections in general, is the ability of the virus to go into a latent state of replication, where it produces very little gene products, and avoids host immune responses. Understanding the parameters of latent infectious phases of herpesviruses is necessary if substantial progress is to be made in treating all herpes virus infections. Additionally, understanding the mechanisms of latency in one herpes virus will provide insight on the mechanisms of all herpes virus, since they are evolutionarily related. With this in mind, the purpose of our research is to understand the molecular mechanisms that transition herpesviruses from a latent phase of replication, to a more productive, lytic phase. Specifically, we are asking what the role of the hCMV tegument protein UL25 was in the latent phase of replication. UL25 is a protein known to impact chromatin structure, transcription activation, and p53 inhibition. To understand hCMVs role in latent replication, we are designing UL25 deficient recombinants of clinical hCMV strains. After recovering and characterizing the recombinant virus lacking UL25, we will measure expression of marker genes for latent infection in cells quiescently infected with either wild‐type or UL25 deficient hCMV strains to see if UL25 plays a significant role in the maintenance or establishment of latency using cell culture models of quiescent infections.