Presence of Epstein-Barr virus and human herpesvirus 6B DNA in multiple sclerosis patients: associations with disease activity

Höllsberg, Per; Kusk, Mette Lind; Bech, Einar; Hansen, Hans J.; Jakobsen, Johannes; Haahr, S

doi:10.1111/j.1600-0404.2005.00516.x

Cited by 53 publications

(56 citation statements)

References 44 publications

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“…Since valaciclovir is a nucleoside analogue, which inhibits the viral polymerase and thereby replication of the virus, it was not surprising that treatment with valaciclovir did not significantly reduce the number of samples with detectable HHV-6B DNA or EBV DNA in plasma. In contrast, treatment with valaciclovir reduced EBV DNA in saliva [67]. After 20 weeks of treatment, no EBV DNA was demonstrated in the saliva, which remained negative for an additional 8 weeks, including 4 weeks after stopping treatment.…”

Section: Controlled Trials Of Antiviral Chemotherapymentioning

confidence: 61%

“…After 20 weeks of treatment, no EBV DNA was demonstrated in the saliva, which remained negative for an additional 8 weeks, including 4 weeks after stopping treatment. Valaciclovir did not have an effect on HHV-6B DNA in saliva [67]. Multiplication of EBV takes place in the epithelial cells of the oropharynx.…”

Section: Controlled Trials Of Antiviral Chemotherapymentioning

confidence: 98%

“…There are conflicting data whether the potential involvement of HHV-6 regards the A or B variant. Recently, HHV-6B and EBV DNA were amplified from plasma samples from MS patients and healthy controls using quantitative PCR [67]. The presence in plasma of EBV and/or HHV-6B DNA was significantly correlated to the clinical activity of the disease.…”

Section: Detection Of Virus In Bloodmentioning

confidence: 99%

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Multiple sclerosis is linked to Epstein‐Barr virus infection

Haahr

Höllsberg

2006

Reviews in Medical Virology

111

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The aetiology and pathogenesis of MS are unknown, but environmental agents, genetic susceptibility and stochastic events are likely to be involved. In order to evaluate the possibility that MS is linked to EBV infection, we here evaluate studies on MS- and EBV-epidemiology, prospective and retrospective analysis of EBV-serology, investigations of EBV DNA sequences in blood and tissues, specificity of antibodies in oligoclonal bands in MS patients and results from antiviral chemotherapy of MS patients. It could be demonstrated that EBV is complying with the epidemiological observations in MS and that all MS patients are seropositive to EBV in contrast to healthy controls. Importantly, despite difficulties in diagnosing child-MS, the vast majority of these patients are also EBV seropositive. In contrast to control groups, recent EBV infections have never been observed in children or adults with MS. Further prospective studies indicate a 2.8 times higher tendency for development of MS after infectious mononucleosis. In MS patients, unbiased analyses pull out EBV antigens as high-affinity targets for the antibodies in the oligoclonal bands. Humans are the exclusive natural host for EBV, a finding that may explain why MS is unique to humans. Together these unique observations strongly suggest a linkage between MS and EBV infection. Infection by EBV offers numerable mechanisms to perturb the immune system, including mimicry and superantigen induction, which may potentially participate in the disease mechanisms. In contrast, studies demonstrating higher IgG titres and occurrence of viral DNA in serum/plasma are likely to reflect a consequence of the disease. An explanation for a potential role of respiratory diseases in MS is discussed. It is concluded that the ultimate test to the hypothesis of MS and EBV is the development and application of an EBV vaccine, which is predicted to eradicate the disease.

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Section: Controlled Trials Of Antiviral Chemotherapymentioning

confidence: 61%

Section: Controlled Trials Of Antiviral Chemotherapymentioning

confidence: 98%

Section: Detection Of Virus In Bloodmentioning

confidence: 99%

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Multiple sclerosis is linked to Epstein‐Barr virus infection

Haahr

Höllsberg

2006

Reviews in Medical Virology

111

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“…Studies based on the detection of EBV DNA in serum [41], plasma [29] and mononuclear cells [20,27,28,40] (Table 6) found DNA, both in cases and in controls, but only showed OR: odds ratio; CI: confidence interval; S: selection; C: comparability; E: exposure OR: odds ratio; CI: confidence interval; S: selection; C: comparability; E: exposure a significant association between the virus and the disease in the study by Sotelo et al [40]. The study by Hay and Tenser [28] should be highlighted, with 100% positive results in both cases and controls.…”

Section: Detection Of Ebv Dna In Bloodmentioning

confidence: 99%

Relation between Epstein-Barr virus and multiple sclerosis: analytic study of scientific production

Santiago

Gutiérrez

Sorlózano

et al. 2010

Eur J Clin Microbiol Infect Dis

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Numerous studies have been carried out to determine whether infection by the Epstein-Barr virus (EBV) can be considered as a risk factor for multiple sclerosis (MS). This work is a meta-analysis of casecontrol observational studies published before January 2009 aimed at assessing the degree of association between EBV and MS infections. A Medline electronic database search was carried out using "Epstein-Barr virus" and "multiple sclerosis" as keywords, from which we selected 30 published studies that met our methodology criteria. We found an association between MS and an exposure to EBV, studied by determining the anti-VCA IgG antibodies (odds ratio [OR]=5.5; 95% confidence interval [CI]=3.37-8.81; p<0.0001), anti-complex EBNA IgG (OR=5.4; 95% CI= 2.94-9.76; p<0.0001) and anti-EBNA-1 IgG (OR=12.1; 95% CI=3. 13-46.89; p<0.0001). No significant association could be found when studying anti-EA IgG (OR=1.3; 95% CI=0.68-2.35; p=0.457), EBV DNA in serum (OR= 1.8; p=0.051) and DNA in brain tissues and in cerebrospinal fluid (CSF) (OR=0.9; 95% CI=0.38-2.01; p=0.768). This meta-analysis detected an association between infection by EBV and MS through the investigation of antibodies, mainly anti-EBNA-1, anticomplex EBNA and anti-VCA IgG.

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“…Seven additional studies were classified as B quality without achieving statistical significance. 40,42,44,47,48,50, 51 Hollsberg et al 40 presented only rates without absolute numbers of HHV-6 antibody-positive MS patients and controls, whereas Ma rtin et al 51 did not present any HHV-6 antibody-positive MS patients. The final 2 studies had severe methodological problems and were classified as C quality.…”

Section: Polymerase Chain Reaction Techniquesmentioning

confidence: 99%