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Human herpesvirus-6 and multiple sclerosis: relapsing-remitting versus secondary progressive
Roverto Alvarez-Lafuente1, Virginia de las Heras, Marta García-Montojo
1Servicio de Neurología, Hospital Clínico San Carlos, Madrid 28040, Spain. labesmul@hcsc.es
Abstract:
Recently, it has been suggested that human herpesvirus-6 (HHV-6) may play a role in the pathogenesis of relapsing-remitting multiple sclerosis (RRMS), but there is not enough information related to the role of HHV-6 in secondary-progressive MS (SPMS). To address this question, we evaluated HHV-6 prevalence, active viral replication and viral load measured by quantitative real-time PCR, in DNA and mRNA extracted from peripheral blood mononuclear cells (PBMCs) and DNA extracted from serum; the samples were collected from 31 SPMS and 31 RRMS patients in a one-year follow-up study, and sex- and age-matched controls. The results were as follows: i) We found a statistical significant difference in HHV-6 DNA prevalences between RRMS and SPMS patients in: DNA extracted from PBMCs (P=0.027), DNA extracted from serum (P=0.010) and mRNA extracted from PBMCs (P=0.010). When we compared HHV-6 prevalences from RRMS patients in relapse and in remission with those from SPMS patients, we only achieved a statistical significance for the relapses (P=0.003 in DNA from PBMCs, and P<0.001 in DNA from serum samples and mRNA from PBMCs). ii) We only found HHV-6 variant A among HHV-6 positive samples in serum. iii) We did not find any difference in HHV-6 viral loads. These results suggest that HHV-6A does not play an active role in SPMS, while this virus may contribute to the pathogenesis of RRMS triggering MS attacks in a subset of patients.
Insights
Human herpesvirus-6 (HHV-6) DNA and mRNA are more prevalent in relapsing-remitting multiple sclerosis (RRMS) patients, particularly during relapses. HHV-6A may contribute to RRMS pathogenesis by triggering attacks.
Area of Science:
- Neurovirology
- Immunology
- Infectious Diseases
Background:
- Human herpesvirus-6 (HHV-6) is implicated in multiple sclerosis (MS) pathogenesis.
- Limited data exists on HHV-6's role in secondary-progressive MS (SPMS).
Purpose of the Study:
- To investigate HHV-6 prevalence, replication, and viral load in SPMS and relapsing-remitting MS (RRMS) patients.
- To determine if HHV-6 contributes to MS progression or relapse activity.
Main Methods:
- Quantitative real-time PCR used to analyze HHV-6 DNA and mRNA in PBMCs and serum.
- Samples from 31 SPMS, 31 RRMS patients, and controls were collected over one year.
- HHV-6 variant A identified in serum samples.
Main Results:
- Significantly higher HHV-6 DNA and mRNA prevalence in RRMS patients compared to SPMS patients.
- Prevalence differences were most significant during RRMS relapses.
- No significant differences in HHV-6 viral loads were observed between groups.
Conclusions:
- HHV-6A does not appear to play an active role in SPMS.
- HHV-6 may contribute to RRMS pathogenesis by triggering MS attacks in a subset of patients.
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