Characterization of the Role of Innate Immune Regulators in Control of Gammaherpesvirus Latency
Year: 2025
Type: dissertation
Abstract: Gammaherpesviruses, including Kaposi sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), are DNA viruses that are globally associated with human cancers and establish lifelong latency in the human population. Detection of gammaherpesviral infection by the cGAS-STING innate immune DNA-sensing pathway is critical for suppressing viral reactivation from latency, a process that promotes viral pathogenesis and transmission. We report that barrier-to autointegration factor 1 (BAF)-mediated suppression of the cGAS-STING signaling pathway is necessary for reactivation of KSHV and EBV. We demonstrate a role for BAF in destabilizing cGAS expression and show that inhibiting BAF expression in latently infected, reactivating, or uninfected cells leads to increased type I interferon-mediated antiviral responses and decreased viral replication. Furthermore, BAF overexpression resulted in decreased cGAS expression at the protein level. In this dissertation, I establish BAF as a key regulator of the lifecycle of gammaherpesviruses and a potential target for treating viral infections and malignancies.
DOI: 10.17615/10k2-dt62
Author: Broussard, Grant
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7077459678
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