Vaccination against gammaherpesvirus attenuates viral enhanced disease in a murine model of multiple sclerosis
department or school: Science, Faculty of
department or school: Microbiology and Immunology, Department of
data provider: DSpace
degree campus: UBCV
creator: Rosen, Ariel R.
issued: 2024-06-20T22:25:27Z
issued: 2024
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Multiple Sclerosis (MS) is a chronic, neurodegenerative autoimmune disease of the central nervous system (CNS). The aetiology of the disease remains unknown; however, it is thought to be a combination of environmental factors in genetically susceptible individuals. One such environmental factor is infection with Epstein-Barr virus (EBV), a DNA virus of the gammaherpesvirus family that infects over 95% of individuals worldwide. Following primary infection, EBV establishes a life-long latent infection in the host’s B cells. MS does not develop in the absence of EBV exposure, and EBV is necessary, but insufficient on its own, to cause disease. In a mouse model of EBV and MS, latent infection of mice with γ-herpesvirus-68 (γHV68), the murine homologue of EBV, exacerbates the clinical and immunological outcomes of experimental autoimmune encephalomyelitis (EAE), a common mouse model for MS. The compelling evidence supporting EBV infection as a co-factor in the development of MS has sparked interest in the potential of EBV-targeted therapies to treat the disease, for example by preventing or controlling primary EBV infection using a prophylactic vaccine. As such, mice were vaccinated against, and then challenged with, γHV68, which successfully reduced the viral load of γHV68 latent infection. Mice were subsequently induced with EAE. Vaccinated mice displayed an attenuation of viral-enhanced disease, and early in the course of EAE, vaccinated mice displayed significantly reduced CNS immune infiltration compared to unvaccinated mice. This work demonstrates the potential for vaccination against EBV to prevent or ameliorate MS and highlights the urgency and necessity for the development of an EBV vaccine.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/88496
note: VACCINATION AGAINST GAMMAHERPESVIRUS ATTENUATES VIRAL ENHANCED DISEASE IN A MURINE MODEL OF MULTIPLE SCLEROSIS by Ariel R. Rosen B.Sc., The University of British Columbia, 2022 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Microbiology and Immunology) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) June 2024 © Ariel R. Rosen, 2024 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the thesis entitled: Vaccination against gammaherpesvirus attenuates viral enhanced disease in a murine model of multiple sclerosis submitted by Ariel R. Rosen in partial fulfilment of the requirements for the degree of Master of Science in Microbiology and Immunology Examining Committee: Dr. Marc Horwitz, Professor, Dept. of Microbiology and Immunology, UBC Supervisor Dr. Lisa Osborne, Associate Professor, Dept. of Microbiology and Immunology, UBC Supervisory Committee Member Dr. Maria Tokuyama, Assistant Professor, Dept. of Microbiology and Immunology, UBC Additional Examiner Additional Supervisory Committee Members: Dr. Laura Sly, Professor, Dept. of Pediatrics – Div. of Gastroenterology, UBC Supervisory Committee Member iii Abstract Multiple Sclerosis (MS) is a chronic, neurodegenerative autoimmune disease of the central nervous system (CNS). The aetiology of the disease remains unknown; however, it is thought to be a combination of environmental factors in genetically susceptible individuals. One such environmental factor is infection with Epstein-Barr virus (EBV), a DNA virus of the gammaherpesvirus family that infects over 95% of individuals worldwide. Following primary infection, EBV establishes a life-long latent infection in the host’s B cells. MS does not develop in the absence of EBV exposure, and EBV is necessary, but insufficient on its own, to cause disease. In a mouse model of EBV and…
has type: Thesis/Dissertation
date issued: 2024-11
is shown at: 10.14288/1.0444003
language: eng
degree discipline: Microbiology and Immunology
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Horwitz, Marc S.
type: Text
identifier URI: http://hdl.handle.net/2429/88496