A Novel Rabbit Model of EBV Infection to Understand the Role of the Virus in the Pathogenesis Multiple Sclerosis

Gulfaraz Khan, Asma Hassani, Narendran Reguraman, Pretty Philip, Safa Shehab

Research output: Contribution to journalConference articlepeer-review

Abstract

Background/Objective(s): Epstein-Barr virus (EBV) is a common herpesvirus associated with a number of different conditions. An accumulating body of evidence indicates that EBV also plays a role in the pathogenesis of multiple sclerosis (MS), a chronic autoimmune disease of the central nervous system (CNS). Our previous study on over 1000 brain samples revealed the presence of EBV in the brain of 90% of MS cases. However, how EBV induces the pathology seen in MS has been frustratingly difficult to address, primarily due to the lack of a suitable animal model of EBV infection. Material(s) and Method(s): Animals were dived into two groups. EBV was administered intravenously (IV) to one group, whilst the control group received isotonic saline. After a period of 4 weeks, we sacrificed the animals and collected all major organs. We then conducted a thorough examination of the histopathological changes and viral dynamics in peripheral blood, spleen, brain, and spinal cord, using a variety of molecular and histopathological techniques Result(s): Using the rabbit model, significant insights were gained regarding the role of EBV in the pathogenesis of MS: • IV introduction of EBV led to a systemic infection, with the virus readily detectable in the spleen, peripheral blood mononuclear cells (PBMCs), and plasma. • CNS infection was associated with the level of circulating infected cells and not the load of free virus. • Peripheral infection prompted the formation of distinct inflammatory cellular clusters in the brain and spinal cord. • These clusters were composed of EBV-infected cells, reactive astrocytes, infiltrating lymphocytes, and macrophages. • Demyelination, a hallmark of MS, was observed within these inflammatory clusters. • The expression of EBV latent transcripts, specifically EBER1 and EBNA1, correlated with the levels of proinflammatory cytokines such as interleukin (IL) 1β and IL6. Conclusion(s): Our findings showed, for the first time, a number of important insights into the biology of EBV and its relationship to MS. The rabbit model of EBV infection holds great potential, not only in unraveling the mechanisms of EBV-related diseases, but also in evaluating the effectiveness of vaccines and antiviral treatments against EBV.

Original languageEnglish
Article number105262
JournalMultiple Sclerosis and Related Disorders
Volume80
DOIs
Publication statusPublished - Dec 2023
Event8th MENACTRIMS Congress - Abu dhabi, United Arab Emirates
Duration: Dec 8 2023Dec 9 2023

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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