PMID- 15659422 OWN - NLM STAT- MEDLINE DCOM- 20050328 LR - 20220129 IS - 1460-2156 (Electronic) IS - 0006-8950 (Print) IS - 0006-8950 (Linking) VI - 128 IP - Pt 3 DP - 2005 Mar TI - Early and late HHV-6 gene transcripts in multiple sclerosis lesions and normal appearing white matter. PG - 516-27 AB - Multiple sclerosis is an inflammatory demyelinating disease of the CNS, the aetiology of which is believed to have both genetic and environmental components. We have investigated one of the candidate viruses for the environmental component of multiple sclerosis, the neurotropic human herpesvirus 6 (HHV-6). Utilizing fluorescent in situ hybridization (FISH) techniques, we have examined human post-mortem tissues for the presence of immediate early and late viral gene expression in multiple sclerosis patient normal appearing white matter (NAWM), lesional tissue and normal control brain samples. HHV-6 gene transcription was detected in all tissue samples and was restricted to oligodendrocytes, as determined by double mRNA FISH analysis. Quantitative analysis of viral mRNA expression indicated that both NAWM and lesional multiple sclerosis samples exhibited significantly higher levels of HHV-6 expression compared with the normal control samples. Lesional samples exhibited the highest levels of viral gene expression, with NAWM exhibiting an intermediate level between lesional and control tissues. Immunofluorescence against early and late HHV-6 proteins verified active translation of HHV-6 viral mRNA in oligodendrocytes. Southern blot analysis of nested polymerase chain reactions using extracted genomic DNA and cDNA confirmed the presence of the HHV-6 genome in all individuals, with the active expression profile mirroring the FISH results. The frequent high level of HHV-6 infection in multiple sclerosis samples suggests a possible role in pathogenesis. FAU - Opsahl, Margaret L AU - Opsahl ML AD - University of Glasgow Department of Neurology, Division of Clinical Neurosciences, Institute of Neurological Sciences, Southern General Hospital, Glasgow, UK. FAU - Kennedy, Peter G E AU - Kennedy PG LA - eng GR - 559/MSS_/Multiple Sclerosis Society/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050119 PL - England TA - Brain JT - Brain : a journal of neurology JID - 0372537 RN - 0 (RNA, Messenger) RN - 0 (RNA, Viral) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Cryopreservation MH - Female MH - Gene Expression MH - Genes, Viral MH - Herpesvirus 6, Human/genetics/*isolation & purification MH - Humans MH - In Situ Hybridization, Fluorescence MH - Male MH - Middle Aged MH - Multiple Sclerosis/*virology MH - Oligodendroglia/virology MH - RNA, Messenger/analysis MH - RNA, Viral/analysis MH - Reverse Transcriptase Polymerase Chain Reaction/methods MH - Roseolovirus Infections/*complications/diagnosis MH - Transcription, Genetic PMC - PMC7109784 EDAT- 2005/01/22 09:00 MHDA- 2005/03/29 09:00 PMCR- 2020/04/01 CRDT- 2005/01/22 09:00 PHST- 2005/01/22 09:00 [pubmed] PHST- 2005/03/29 09:00 [medline] PHST- 2005/01/22 09:00 [entrez] PHST- 2020/04/01 00:00 [pmc-release] AID - awh390 [pii] AID - 10.1093/brain/awh390 [doi] PST - ppublish SO - Brain. 2005 Mar;128(Pt 3):516-27. doi: 10.1093/brain/awh390. Epub 2005 Jan 19.