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ABSTRACT: Human herpesvirus (HHV)-6 has been associated with the pathogenesis of multiple sclerosis (MS) on the basis of serologic, molecular, and histopathologic studies. This study sought to determine the distribution of HHV-6 in different MS body fluids, including serum, saliva, urine, and peripheral blood lymphocytes. The study results extend the observation of an increased frequency of HHV-6 DNA in serum of patients with MS to the unique detection of viral sequences in urine of a subset of patients with MS. Moreover, the HHV-6 identified in these cell-free compartments was predominantly the HHV-6A variant, which has been reported to be neurotropic. These results support the hypothesis that HHV-6 may contribute to the MS disease process.
The Journal of Infectious Diseases 12/2000; 182(5):1321-5. · 6.41 Impact Factor
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ABSTRACT: Throughout the years, a long list of viruses has been associated with multiple sclerosis (MS), however no virus to date has been definitively identified as the etiologic agent of this disease. Recently, human herpesvirus 6 (HHV-6), a newly described herpesvirus, has been suggested to play a role in MS based on: immunohistochemical demonstration of HHV-6 in MS plaques, increased antibodies response to HHV-6 in sera and CSF of MS patients, and the demonstration of HHV-6 DNA in the serum of MS patients but not in normal individuals. To extend these observations we have focused our research in multiple directions. We have increased the number of MS patients tested for HHV-6 serum DNA providing confirmation of our previous study. Additionally we have investigated a possible correlation between HHV-6 viremia and clinical activity. Finally to provide insight into the pathogenesis of this disease, we have begun to characterize the cellular immune response of MS patients to HHV-6. Collectively these studies will help to define the role that HHV-6 may play in the pathogenesis of MS.
Journal of NeuroVirology 06/2000; 6 Suppl 2:S85-7. · 2.31 Impact Factor
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S S Soldan, R Berti,
N Salem,
P Secchiero,
L Flamand,
P A Calabresi,
M B Brennan,
H W Maloni,
H F McFarland,
H C Lin,
M Patnaik,
S Jacobson
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ABSTRACT: Viruses have long been suggested to be involved in the etiology of multiple sclerosis (MS). This suggestion is based on (1) epidemiological evidence of childhood exposure to infectious agents and increase in disease exacerbations with viral infection; (2) geographic association of disease susceptibility with evidence of MS clustering; (3) evidence that migration to and from high-risk areas influences the likelihood of developing MS; (4) abnormal immune responses to a variety of viruses; and (5) analogy with animal models and other human diseases in which viruses can cause diseases with long incubation periods, a relapsing-remitting course, and demyelination. Many of these studies involve the demonstration of increased antibody titers to a particular virus, whereas some describe isolation of virus from MS material. However, no virus to date has been definitively associated with this disease. Recently, human herpesvirus 6 (HHV-6), a newly described beta-herpes virus that shares homology with cytomegalovirus (CMV), has been reported to be present in active MS plaques. In order to extend these observations, we have demonstrated increased IgM serum antibody responses to HHV-6 early antigen (p41/38) in patients with relapsing-remitting MS (RRMS), compared with patients with chronic progressive MS (CPMS), patients with other neurologic disease (OND), patients with other autoimmune disease (OID), and normal controls. Given the ubiquitous nature of this virus and the challenging precedent of correlating antiviral antibodies with disease association, these antibody studies have been supported by the detection of HHV-6 DNA from samples of MS serum as a marker of active viral infection.
Nature Medicine 01/1998; 3(12):1394-7. · 22.46 Impact Factor