Absence of Epstein-Barr virus in the brain and CSF of patients with multiple sclerosis.
OBJECTIVE
Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that becomes latent in B-lymphocytes and has been implicated in the pathogenesis of multiple sclerosis (MS). We searched for latent and active EBV infection in MS brain and CSF.


METHODS
Nested and non-nested real-time PCR were used to detect cell-specific and EBV-specific transcripts in 15 fresh-frozen and 5 formalin-fixed paraffin-embedded MS plaques and in single MS CSF B-lymphocytes and plasma cells. Intrathecal anti-EBV antibody synthesis was measured by ELISA. Immunocytochemistry was used to detect binding of MS CSF and recombinant antibodies (rAbs) generated from clonally expanded plasma cells in MS CSF to EBV-infected cells.


RESULTS
No EBV RNA was found in MS CSF B-lymphocytes or plasma cells. In active MS plaques, EBV-encoded RNA (EBER)-1 was the only and rarely detected transcript. The frequency of detected intrathecal anti-EBV antibody synthesis in patients with MS did not differ from that in non-MS inflammatory CNS disease control patients. Anti-EBV antibodies were detected in the CSF of patients with MS, but MS rAbs did not react with EBV.


CONCLUSIONS
Application of real-time PCR to multiple sclerosis brain and single B-lymphocytes in CSF did not reveal any evidence of active Epstein-Barr virus infection.
Sargsyan
S A
SA
Department of Neurology,University of Colorado Denver School of Medicine, Aurora, CO 80045, USA.
Shearer
A J
AJ
Ritchie
A M
AM
Burgoon
M P
MP
Anderson
S
S
Hemmer
B
B
Stadelmann
C
C
Gattenlöhner
S
S
Owens
G P
GP
Gilden
D
D
Bennett
J L
JL
D001402:B-Lymphocytes / Q000821:virology; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000473:pathology* / Q000503:physiopathology / Q000821:virology*; D002555:Cerebrospinal Fluid / Q000166:cytology; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000473:pathology* / Q000821:virology*; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics
D015415:Biomarkers; C099537:Epstein-Barr virus encoded RNA 1; D012367:RNA, Viral; D014764:Viral Proteins