Unraveling the cellular and viral genes important for fully productive Marek’s disease virus replication

Marek’s disease (MD), caused by Marek’s disease herpesvirus (MDV), is a fatal lymphoproliferative disease of chickens. MDV has a significant impact on the poultry industry, with marked economic losses due to the high morbidity and mortality rates. The virus enters the host through inhalation of cell-free MD virions in the poultry house that have been previously produced by the feather follicle epithelial (FFE) cells of infected birds. Once in the host, it can establish latency in CD4+ T lymphocytes. Current vaccines only reduce the pathologic changes and tumorigenesis but do not prevent virus replication, shedding, and the subsequent latency. Plus, leaky vaccines put evolutionary pressure onto the virus resulting in more virulent MDV outbreaks during the past decades. For these reasons, improved vaccines or treatments for the disease are needed. The MDV-transformed chicken cells (MDCCs) are an excellent model for understanding herpesvirus pathogeneses and filling the current knowledge gap of viral replication, latency, and transformation. The research described in this thesis provides a novel ex vivo model to study MDV replication, latency, transformation, and reactivation. First, we have shown an easy, feasible way to isolate and maintain MDCCs ex vivo for over a year. Secondly, we present a temperature treatment assay to induce MDV reactivation in MDCCs using a fluorescently tagged virus. Thirdly, by using MDV in which early and late viral proteins are tagged with fluorescence proteins, combined with the MDCC ex vivo model, we were able to identify novel host and viral gene responses during different phases of MDV replication using flow cytometry, cell sorting, and RNA sequencing. In summary, these studies advance our knowledge regarding MDV replication, latency, transformation, and reactivation, which will help to improve the current strategy of vaccination and treatment plans in the poultry industry. Importantly, this work is also translatable to Epstein-Barr and Kaposi sarcoma-associated viruses that cause human lymphoproliferative disease.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

VMS - Pathobiology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2023

Author dc:creator

• Tien, Yung-Tien

Contributors dc:contributor

• Jarosinski, Keith
• Rock, Dan
• Vieson, Miranda
• Brooke, Christopher

• Marek's Disease
• Reactivation

Statement dc:rights

• Copyright 2023 Yung-Tien Tien

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/121197

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F121197