Plaque-associated expression of human herpesvirus 6 in multiple sclerosis.

TLDR

Representational difference analysis and immunocytochemistry with monoclonal antibodies against HHV‑6 virion protein 101K and DNA binding protein p41 were employed to detect and localize viral sequences and proteins in multiple sclerosis brain tissue. PCR and sequencing revealed that HHV‑6, predominantly variant B group 2, is present in over 70 % of multiple sclerosis and control brains, with immunocytochemistry showing oligodendrocyte and neuronal staining around plaques in MS cases, suggesting a potential role for HHV‑6 in MS pathogenesis.

Abstract

Representational difference analysis was used to search for pathogens in multiple sclerosis brains. We detected a 341-nucleotide fragment that was 99.4% identical to the major DNA binding protein gene of human herpesvirus 6 (HHV-6). Examination of 86 brain specimens by PCR demonstrated that HHV-6 was present in > 70% of MS cases and controls and is thus a commensal virus of the human brain. By DNA sequencing, 36/37 viruses from MS cases and controls were typed as HHV-6 variant B group 2. Other herpesviruses, retroviruses, and measles virus were detected infrequently or not at all. HHV-6 expression was examined by immunocytochemistry with monoclonal antibodies against HHV-6 virion protein 101K and DNA binding protein p41. Nuclear staining of oligodendrocytes was observed in MS cases but not in controls, and in MS cases it was observed around plaques more frequently than in uninvolved white matter. MS cases showed prominent cytoplasmic staining of neurons in gray matter adjacent to plaques, although neurons expressing HHV-6 were also found in certain controls. Since destruction of oligodendrocytes is a hallmark of MS, these studies suggest an association of HHV-6 with the etiology or pathogenesis of MS.