Age- and Disease-Dependent HERV-W Envelope Allelic Variation in Brain Association with Neuroimmune Gene Expression 英文参考文献.docVIP
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Age- and Disease-Dependent HERV-W Envelope Allelic Variation in Brain Association with Neuroimmune Gene Expression 英文参考文献
Age-andDisease-DependentHERV-WEnvelopeAllelic
VariationinBrain:AssociationwithNeuroimmuneGene
Expression
RakeshK.Bhat1,KristoforK.Ellestad1,B.MattWheatley2,ReneWarren3,RobertA.Holt3 ,Christopher
Power1*
1Division of Neurology, University of Alberta, Edmonton, Alberta, Canada, 2Division of Neurosurgery, University of Alberta, Edmonton, Alberta, Canada, 3British
ColumbiaCancerAgency,GenomeScienceCentre,Vancouver,BritishColumbia,Canada
Abstract
Background: The glycoprotein, Syncytin-1, is encoded by a human endogenous retrovirus (HERV)-W env gene and is
capableofinducingneuroinflammation.Thespecificallele(s)responsibleforSyncytin-1expressioninthebrainisuncertain.
Herein,HERV-WenvdiversitytogetherwithSyncytin-1abundanceandhostimmunegeneprofileswereexaminedinthe
nervoussystemusingamultiplatformapproach.
Results: HERV-W env sequences were encoded by multiple chromosomal encoding loci in primary human neurons
comparedwithlesschromosomaldiversityinastrocytesandmicroglia(p,0.05).HERV-WenvRNAsequencesclonedfrom
brainsofpatientswithsystemicorneurologicdiseaseswereprincipallyderivedfromchromosomallocus7q21.2.Withinthe
same specimens, HERV-W env transcript levels were correlated with the expression of multiple proinflammatory genes
(p,0.05). Deep sequencing of brain transcriptomes disclosed the env transcripts to be the most abundant HERV-W
transcripts, showing greater expression in fetal compared with healthy adult brain specimens. Syncytin-1’s expression in
healthybrainspecimenswasderivedfrommultipleencodinglociandlinkedtodistinctimmuneanddevelopmentalgene
profiles.
Conclusions:Syncytin-1expressioninthebrainduringdiseasewasassociatedwithneuroinflammationandwasprincipally
encodedbyafulllengthprovirus.ThepresentstudiesalsohighlightedthediversityinHERVgeneexpressionwithinthe
brainandreinforcethepotentialcontributionsofHERVexpressiontoneuroinflammatorydiseases.
Citation:BhatRK,EllestadKK,WheatleyBM,WarrenR,HoltRA,etal.(2011)Age-andDisease-DependentHERV-WEnvelopeAllelicVariationinB
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