title: ERV-3 envelope expression and congenital heart block: what does a physiological knockout teach us.
abstract: Congenital heart block is a serious condition with significant mortality due in most cases to the transplacental transfer of autoantibodies from an otherwise asymptomatic mother. Although SSA/Ro and SSB/La autoantibodies have been implicated, attention has focused recently on autoantibodies to envelope proteins of endogenous retrovirus-3 (ERV-3). We have recently identified in 1% of the caucasian population a natural knock out of ERV-3 due to a premature stop mutation generating a severely truncated form of the protein [corrected]. If a pregnant female homozygous for the truncated form of the ERV-3 carries a foetus expressing the entire protein, the mother might be expected to acquire high titre immunity, while the foetus homozygous for the truncated form would not be expected to immunise its mother. In order to test whether this naturally occurring model could shed light on the pathogenesis of CHB, we determined the status of the ERV-3 stop polymorphism in 12 mothers of CHB infants [corrected]. The fact that none was homozygous for the stop mutation tends to rule out a role for the stop polymorphism of the mothers in the generation of the CHB disease, but does not exclude that other polymorphisms might be involved [corrected].
authors.affiliation: Unité Rétrovirus Endogènes et Eléments Rétroïdes des Eucaryotes Supérieurs, CNRS UMR 1573, Institut Gustave Roussy, Villejuif, France.
authors.forename: N
authors.initials: N
authors.lastname: de Parseval
authors.forename: G
authors.initials: G
authors.lastname: Forrest
authors.forename: P J
authors.initials: PJ
authors.lastname: Venables
authors.forename: T
authors.initials: T
authors.lastname: Heidmann
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity; D020077:Endogenous Retroviruses / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D005315:Fetal Diseases / Q000276:immunology; D005318:Fetal Heart / Q000276:immunology*; D015752:Genes, env; D005838:Genotype; D006327:Heart Block / Q000151:congenital* / Q000196:embryology / Q000276:immunology; D006329:Heart Conduction System / Q000276:immunology / Q000473:pathology; D006801:Humans; D007112:Immunity, Maternally-Acquired; D007231:Infant, Newborn; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D051379:Mice; D018448:Models, Immunological; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011247:Pregnancy; D013728:Terminator Regions, Genetic; D014327:Trophoblasts / Q000276:immunology / Q000821:virology; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D007518:Isoantibodies; D014759:Viral Envelope Proteins; C120973:envelope protein, endogenous retrovirus-3