Tissue Distribution and Variant Characterization of Human Herpesvirus (HHV)–6: Increased Prevalence of HHV‐6A in Patients with Multiple Sclerosis

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.

Members 6B and 14 of the TNF receptor superfamily in multiple sclerosis predisposition

“…[25][26][27] Increased prevalence of HHV6 DNA levels in serum 28,29 and RNA/DNA levels in peripheral blood mononuclear cells 30 have been associated with exacerbations in relapsing-remitting MS. A cellular receptor for HHV6 is the complement regulatory protein CD46; 9 however, as already mentioned, all the molecular players involved in viral entry may not be described yet. Therefore, one of those entry helpers could be encoded by the TNFRSF14 gene and, as shown by the present data, a polymorphism, which was previously associated with rheumatoid arthritis susceptibility has also demonstrated its role in MS predisposition and in HHV6 active replication, as measured by viral DNA levels in serum.…”

B cells in multiple sclerosis

“…Herpesviruses-In the past decade, two human herpesviruses have also been associated with MS. One is human herpesvirus-6 (HHV-6), the cause of roseola, and the other is Epstein-Barr virus (EBV), which causes infectious mononucleosis (88)(89)(90)(91)(92). The detection of fingerprints of these two ubiquitous viruses known to be latent in blood B-(EBV) or T-(HHV-6) cells is intriguing, since the primary encounter with either virus usually occurs before or during puberty, the same time that epidemiologic evidence indicates exposure to the disease-causing agent of MS.…”

Human Herpesvirus 6 Infection as a Trigger of Multiple Sclerosis

“…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.…”

“…39,58 Of the studies classified as B quality, 1 study reached statistical significance, 44 whereas 8 studies did not. 23,47,[59][60][61][62]67,68 In most B-quality studies, a greater proportion of MS patients had detectable HHV-6 DNA in their PBMCs than controls; however, the results were not statistically signifi-For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings a .…”