This study examined the association between HHV-6 infection and multiple sclerosis (MS) and the relationship between HHV-6 reactivation and disease activity. The frequency of HHV-6 genomic sequences in peripheral blood mononuclear cells (PBMCs), the incidence of plasma viremia (nPCR), the transcription of viral mRNA in PBMCs (RT-PCR), the presence of antiviral IgM and IgG class antibodies in the plasma (IFA) of 16 relapsing/remitting and secondary progressive MS patients were studied in comparison with clinical manifestations of the disease, magnetic resonance imaging (MRI) of brain, and serum interleukin (IL)-12 concentrations (ELISA). The prevalence of HHV-6 infection was significantly higher in patients with MS (16/26) than in patients with other neurological diseases (6/21) and in blood donors (43/150). HHV-6 reactivation was found during periods of disease activity with Gadolinium-enhancing lesions on MRI in both relapsing/remitting and secondary progressive MS (10/13; 76.9%). In patients with active MS disease, serum concentrations of IL-12 were significantly higher in those patients with active HHV-6 infection than in patients with latent infection. The data confirm an association between HHV-6 infection and MS and show a correlation between HHV-6 reactivation and disease activity in relapsing/remitting and secondary progressive MS. The risk of an exacerbation of MS was significantly higher (P < 0.005) in patients with active HHV-6 infection than in patients with latent infection. A clear correlation between HHV-6 reactivation and serum IL-12 concentrations during disease activity has been demonstrated. The results suggest that HHV-6 reactivation is implicated in exacerbation of MS, possibly through modulation of IL-12 synthesis.
Copyright 2003 Wiley-Liss, Inc.