Multiple sclerosis (MS) is a chronic neuroinflammatory condition of the
central nervous system (CNS). It is a major cause of neurological
disability in young adults, particularly women. What triggers the
destruction of myelin sheaths covering nerve fibres is unknown. Both
genetic and infectious agents have been implicated. Of the infectious
agents, Epstein-Barr virus (EBV), a common herpesvirus, has the
strongest epidemiological and serological evidence. However, the
presence of EBV in the CNS and demonstration of the underlying
mechanism(s) linking EBV to the pathogenesis of MS remain to be
elucidated. We aimed at understanding the contribution of EBV infection
in the pathology of MS. We examined 1055 specimens (440 DNA samples and
615 brain tissues) from 101 MS and 21 non-MS cases for the presence of
EBV using PCR and EBER-in situ hybridization (EBER-ISH). EBV was
detected by PCR and/or EBER-ISH in 91/101 (90%) of MS cases compared to
only 5/21 (24%) of non-MS cases with other neuropathologies. None of the
samples were PCR positive for other common herpesviruses (HSV-1, CMV,
HHV-6). By quantitative PCR, EBV viral load in MS brain was mainly low
to moderate in most cases. However, in 18/101 (18%) of MS cases,
widespread but scattered presence of EBV infected cells was noted in the
affected tissues by EBER-ISH. Immunohistochemical analysis of EBV gene
expression in the 18 heavily infected cases, revealed that the EBV
latent protein EBNA1, and to a lesser extent the early lytic protein
BZLF1 were expressed. Furthermore, using double-staining we show for the
first time that astrocytes and microglia, in addition to B-cells can
also be infected. To the best of our knowledge, this is the most
comprehensive study demonstrating that EBV is present and
transcriptionally active in the brain of most cases of MS and supports a
role for the virus in MS pathogenesis. Further studies are required to
address the mechanism of EBV involvement in MS pathology.
central nervous system (CNS). It is a major cause of neurological
disability in young adults, particularly women. What triggers the
destruction of myelin sheaths covering nerve fibres is unknown. Both
genetic and infectious agents have been implicated. Of the infectious
agents, Epstein-Barr virus (EBV), a common herpesvirus, has the
strongest epidemiological and serological evidence. However, the
presence of EBV in the CNS and demonstration of the underlying
mechanism(s) linking EBV to the pathogenesis of MS remain to be
elucidated. We aimed at understanding the contribution of EBV infection
in the pathology of MS. We examined 1055 specimens (440 DNA samples and
615 brain tissues) from 101 MS and 21 non-MS cases for the presence of
EBV using PCR and EBER-in situ hybridization (EBER-ISH). EBV was
detected by PCR and/or EBER-ISH in 91/101 (90%) of MS cases compared to
only 5/21 (24%) of non-MS cases with other neuropathologies. None of the
samples were PCR positive for other common herpesviruses (HSV-1, CMV,
HHV-6). By quantitative PCR, EBV viral load in MS brain was mainly low
to moderate in most cases. However, in 18/101 (18%) of MS cases,
widespread but scattered presence of EBV infected cells was noted in the
affected tissues by EBER-ISH. Immunohistochemical analysis of EBV gene
expression in the 18 heavily infected cases, revealed that the EBV
latent protein EBNA1, and to a lesser extent the early lytic protein
BZLF1 were expressed. Furthermore, using double-staining we show for the
first time that astrocytes and microglia, in addition to B-cells can
also be infected. To the best of our knowledge, this is the most
comprehensive study demonstrating that EBV is present and
transcriptionally active in the brain of most cases of MS and supports a
role for the virus in MS pathogenesis. Further studies are required to
address the mechanism of EBV involvement in MS pathology.
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