Honors Program
Honors Program: Embargoed Theses
First Advisor
Dr. Lindsey Crawford
Second Advisor
Dr. Kimberly Hansen
Date of this Version
Spring 3-31-2025
Document Type
Thesis
Citation
Bryant, A. 2025. Immunosenescence and HCMV: the Interaction Between UL2 and the Human Gene HMGCS1. Undergraduate Honors Thesis. University of Nebraska-Lincoln.
Abstract
Human Cytomegalovirus (HCMV) is a common (40-90% worldwide infection) ß-herpesvirus. Previous studies have drawn a potential link between HCMV and the phenomenon known as immunosenescence, in which mammalian cells experience a decrease in cellular activity and proliferation. During HCMV infection, cells of the myeloid lineage are a site of viral replication and dissemination, important for both lifelong infection and a biphasic viral lifecycle. During latency (1): the virus is dormant, minimal viral proteins are expressed; and during reactivation (2): the virus begins replicating again and produces new virus particles. Following latency, HCMV reactivates in macrophages by controlling cell cycle regulation leading to widespread viral replication and spread. This balance between viral latency and reactivation is important to disease development. Prior proteomics analysis by others found that UL2, an HCMV RL11 protein with unknown function, directly interacts with human proteins HMGCS1 and CREBBP. We intended to look at how UL2 interacted with HMGCS1 during HCMV latency and reactivation in monocytes. This study aimed to explore whether these interactions contribute to immunosenescence as is seen in patients with HCMV. We hypothesize that UL2 will cause a decrease in abundance of HMGCS1 protein and increase cell cycle arrest and would lead to abnormal cells. After looking at the role UL2 plays in the HCMV lifecycle, we know that it is not involved in lytic replication. We also built a molecular tool to express UL2 for examining these cellular interactions. Moving forward, we will characterize the interactions that UL2 has with HMGCS1 in monocytes and determine whether they contribute to immunosenescence and viral reactivation.
Comments
Copyright Amara Bryant 2025.