Presence of Epstein-Barr virus and human herpesvirus 6B DNA in multiple sclerosis patients: associations with disease activity.
OBJECTIVE
To assess the presence of Epstein-Barr virus (EBV) and human herpesvirus 6B (HHV-6B) DNA in saliva and plasma from multiple sclerosis (MS) patients enrolled in a randomized, double-blind, placebo-controlled valacyclovir treatment study.


METHODS
DNA was prepared following ultracentrifugation of saliva and plasma. EBV and HHV-6B DNAs were determined by real-time polymerase chain reaction.


RESULTS
EBV and HHV-6B DNAs were detected in 41% and 65% of saliva samples, respectively. In patients treated with valacyclovir, the percentage of saliva samples with EBV was significantly reduced (9%; P = 0.000017), whereas the frequency of HHV-6B positive samples was unchanged (57%; P = 0.38). Longitudinal studies demonstrated a time-dependent reduction in the frequency of saliva samples containing EBV following valacyclovir treatment. In contrast, plasma contained EBV and HHV-6B DNAs in 17% and 25% of the samples, respectively, and these numbers were not significantly reduced following valacylovir treatment (13% and 16%, respectively), nor were they different from those of healthy controls (6% and 39%, respectively). Patients with high disease activity had a significantly higher frequency of EBV (P = 0.018) and HHV-6B (P = 0.023) positive samples than did patients with low disease activity. The presence of EBV and HHV-6B was strongly correlated in plasma (P < 0.00000001), but not in saliva (P = 0.41).


CONCLUSIONS
MS patients express EBV and HHV-6B in both saliva and plasma, but only the expression of EBV in saliva is significantly reduced following valacyclovir treatment. Although EBV and HHV-6B DNAs can be detected in plasma from healthy individuals, the co-expression of both these viruses in MS patients is highly significant and further associated with clinical activity. The observations of viral DNA in plasma are consistent with an underlying immunologic defect in MS.
Höllsberg
P
P
Institute of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark. ph@microbiology.au.dk
Kusk
M
M
Bech
E
E
Hansen
H J
HJ
Jakobsen
J
J
Haahr
S
S
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics*; D015654:Herpesvirus 6, Human / Q000235:genetics*; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000821:virology*; D012463:Saliva / Q000821:virology; D013223:Statistics as Topic; D016896:Treatment Outcome; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019562:Viral Load
D000998:Antiviral Agents; D004279:DNA, Viral; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir