Role of Epstein - Barr virus In the Pathogenesis Of Multiple Sclerosis

Asma Hassani


Multiple sclerosis (MS) is a chronic pathology of the central nervous system,

characterized by inflammation, demyelination and neurodegeneration. The prevalence and incidence rates of MS are on the rise worldwide. What causes MS is unknown. However, it is widely accepted that MS occurs in genetically susceptible individuals exposed to certain environmental factors Sero - epidemiological data suggest a strong association between Epstein-Barr virus (EBV) and MS. EBV is one of the commonest viruses in the human population with ~90% global sero --positivity. EBV infects naive B cells and immortalizes them. While some postmortem studies have shown EBV in MS lesions, others have failed to reach similar observation. Variation in technical approaches and sample size could be the reason for reported inconsistencies. Thus, we have assessed the hypothesis that EBV may enter MS brain and contribute to disease pathogenesis. Four objectives were highlighted in this thesis: to investigate EBV presence in MS brain using large sample size, quantify EBV viral load in brain tissues, determine possible route of virus entry to the brain, and

determine viral gene expression in MS brain. In a case-control design, 122 MS and non-MS cases were studied and compared. Formalin stored brain coronal slices were received from Rocky Mountain MS Centre, US. DNA extraction was optimized and PCR amplification of EBV Bam HI was performed to determine EBV presence/ absence in the brain. EBV viral load was quantified in infected cases using qPCR. Localization of infected cells was achieved using EBER in situ hybridization, and viral gene expression was determined using immunohistochemistry. The phenotype of EBV infected cells was characterized using immunohistochemistry for cellular markers. EBV DNA was detected in 90% MS and 24% non-MS cases. EBV

infected cells were more prevalent in brain parenchyma than in meninges, expressing latent EBNA1 and lytic BZLF1. EBV infected cells were likely to have B lymphocyte phenotype. We concluded that EBV differential presence in MS brain reflected a pathogenic contribution to MS. Further studies are warranted to determine the mechanism of EBV involvement in MS Pathogenesis.