Abstract
Recent studies have focused on the associations between human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7), and multiple sclerosis (MS). The aim of this study was to investigate the associations between HHV-6 and HHV-7 reactivation and MS disease activity, and interleukin 12 (IL-12) and tumor necrosis factor α (TNF-α) production. The frequency of plasma viremia by nested polymerase chain reaction and transcription of viral mRNA in peripheral blood mononuclear cells by reverse transcriptase-polymerase chain reaction (RT-PCR) of 14 relapsing/remitting (RR) and 14 secondary progressive (SP) MS patients were studied in comparison with clinical manifestation of the disease. Serum concentrations of cytokines IL-12 and TNF-α were analyzed by enzyme-linked immunosorbent assay. Plasma samples from 25 of the 28 MS patients with estimated latent/persistent HHV-6 and/or HHV-7 infection were examined during relapse and remission/relative remission. HHV-6 reactivation was found in 4 of the 7 RRMS and 4 of the 7 SPMS patients, and HHV-7 reactivation was identified in 3 of the 7 RRMS and 1 of the 7 SPMS patients (all in relapse). In 2 of the 3 RRMS patients without viremia in relapse, HHV-6 mRNA transcription was detected. In RRMS and SPMS patients with active HHV-6 and HHV-7 infection in relapse, the serum concentrations of IL-12 and TNF-α were significantly higher than in those with latent virus infection. HHV-6 and HHV-7 reactivation could be implicated in the exacerbation of MS via activation of Th1 lymphocyte subsets.
Highlights
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system, the etiology of which is thought to have a possible viral component
This study examined the relationship between the reactivation of both closely related human herpesviruses human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) and disease activity in relapsing/remitting (RR) and secondary progressive (SP) MS
The transcription of viral mRNA was detected in 2 of the 3 peripheral blood mononuclear cells (PBMCs) RNA samples from relapsing-remitting MS (RRMS) patients in an exacerbation phase confirmed by brain Magnetic resonance imaging (MRI), but without HHV-6 plasma viremia
Summary
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system, the etiology of which is thought to have a possible viral component. The balance between proinflammatory and anti-inflammatory cytokines has been shown to be associated with the disease activity in MS [14]. Th1-type cells producing disease-promoting proinflammatory cytokines, Our previously studies have shown the association of HHV-6 with MS and correlation between HHV-6 reactivation and MS disease activity [17, 18]. Active HHV-7 infection was found more frequently in MS patients than control blood donors, its possible involvement in demyelinating processes has to be elucidated [17, 19]. This study examined the relationship between the reactivation of both closely related human herpesviruses HHV-6 and HHV-7 and disease activity in relapsing/remitting (RR) and secondary progressive (SP) MS. Plasma viremia and transcription of viral mRNA in PBMCs were used as the markers of HHV-6 and HHV-7 active infection, and they correlated with clinical and MRI evidence of MS activity as well as Medicina (Kaunas) 2011;47(10)
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