The regulation and role of glycoprotein C during herpesvirus pathogenesis

Within the Herpesviridae, the Alphaherpesvirinae is a subfamily that infects a broad number of mammals, birds, and other vertebrates, causing diseases that affect humans and companion and agricultural animals. Marek’s disease (MD) is a lymphoproliferative disease of chickens with high mortality rates caused by Marek’s disease herpesvirus (MDV). Infections with virulent MDV strains incur severe economic losses due to high mortality rates, and prevention/vaccination against MD. MDV infects immune cells that circulate to the skin where they transfer the virus to feather follicle epithelial (FFE) cells. It is at this site where fully productive MDV replication occurs, and the virus is shed from the chickens into the environment that can then infect naïve chickens through inhalation of infectious dust and dander. Current vaccination against MD only reduces clinical signs and oncogenesis but does not prevent virus replication, shedding, and the subsequent establishment of latency. This presents an obstacle for controlling the disease, especially on poultry farms where even vaccinated chickens can continue to shed virulent virus. Previous research in our laboratory showed that the alphaherpesvirus conserved glycoprotein C (gC) is essential for horizontal transmission of MDV in chickens. We hypothesize that gC is a potential target to be used in the development of recombinant vaccines that can provide more efficient and effective protection against clinical signs, replication, and transmission of the virus. The research described in this thesis provides more insight on the regulation and the mechanistic roles gC proteins play during horizontal transmission of alphaherpesviruses. First, the regulation of MDV gC by the MDV-specific RLORF4 gene was studied and was conclusively shown that RLORF4 is not involved in regulation of gC expression. Secondly, the requirement of gC for homologous avian herpesviruses during horizontal transmission was addressed showing gC is also required for an MD vaccine strain that is homologous to MDV. Thirdly, the conserved function of avian gC proteins was studied using classical gene exchange experiments where both complete and deficient compensation during horizontal transmission in chickens allowed us to elucidate potential conserved functions of gC proteins. In summary, these studies advance our knowledge regarding herpesvirus pathogenesis that may improve vaccine development against human and agricultural diseases.

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

2022

Author dc:creator

• Vega Rodriguez, Widaliz

Contributors dc:contributor

• Jarosinski, Keith W
• Lau, Gee
• Whitaker, Rachel
• Fang, Ying

• alphaherpesviruses
• avian
• gC
• transmission
• splicing

Statement dc:rights

• Copyright 2022 Widaliz Vega Rodriguez

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/115342

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F115342