title: Age- and disease-dependent HERV-W envelope allelic variation in brain: association with neuroimmune gene expression.
abstract: BACKGROUND
  The glycoprotein, Syncytin-1, is encoded by a human endogenous retrovirus (HERV)-W env gene and is capable of inducing neuroinflammation. The specific allele(s) responsible for Syncytin-1 expression in the brain is uncertain. Herein, HERV-W env diversity together with Syncytin-1 abundance and host immune gene profiles were examined in the nervous system using a multiplatform approach.
  
  
  RESULTS
  HERV-W env sequences were encoded by multiple chromosomal encoding loci in primary human neurons compared with less chromosomal diversity in astrocytes and microglia (p<0.05). HERV-W env RNA sequences cloned from brains of patients with systemic or neurologic diseases were principally derived from chromosomal locus 7q21.2. Within the 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 healthy brain specimens was derived from multiple encoding loci and linked to distinct immune and developmental gene profiles.
  
  
  CONCLUSIONS
  Syncytin-1 expression in the brain during disease was associated with neuroinflammation and was principally encoded by a full length provirus. The present studies also highlighted the diversity in HERV gene expression within the brain and reinforce the potential contributions of HERV expression to neuroinflammatory diseases.
authors.affiliation: Division of Neurology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Bhat
authors.forename: Kristofor K
authors.initials: KK
authors.lastname: Ellestad
authors.forename: B Matt
authors.initials: BM
authors.lastname: Wheatley
authors.forename: Rene
authors.initials: R
authors.lastname: Warren
authors.forename: Robert A
authors.initials: RA
authors.lastname: Holt
authors.forename: Christopher
authors.initials: C
authors.lastname: Power
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000483:Alleles; D001921:Brain / Q000196:embryology / Q000821:virology*; D020077:Endogenous Retroviruses / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D015686:Gene Products, env / Q000096:biosynthesis; D015752:Genes, env; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D007107:Immune System; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000473:pathology; D011257:Pregnancy Proteins / Q000096:biosynthesis; D017423:Sequence Analysis, RNA
chemical_list: D015686:Gene Products, env; D011257:Pregnancy Proteins; C405335:syncytin