Sequence similarity and structural homologies are involved in the autoimmune response elicited by mouse hepatitis virus A59.
The features of autoantibodies (autoAb) to liver fumarylacetoacetate hydrolase (FAH) elicited in mice infected with mouse hepatitis virus (MHV) were studied by ELISA and western-blot competition assays. All sera tested contained Ab to cryptic FAH epitopes according with results from western-blot tests, whereas ELISA data indicated that some of these same sera did recognize native epitopes of the autoantigen (autoAg). Such differences were detected in individual sera from various mouse strains, and were ascribed to the fact that proteins insolubilized on solid supports expose a variety of conformational and cryptic antigenic determinants. On the other hand, whereas results from both experimental protocols showed that anti-MHV Ab did not cross-react with the soluble autoAg, the opposite situation did not show analogous results. Thus, binding of autoAb to insolubilized FAH could be inhibited by MHV depending on the mouse serum or the experimental protocol used. Additionally, a set of synthetic homologous peptides from mouse FAH and various viral proteins was employed to analyze the Ab repertoire of MHV-infected mice. Results indicated that two homologous peptides were recognized by most Ab: the N-terminal sequences (1-10) from FAH and the nucleocapside, both sharing 50% of identity, and sequence 2317-2326 of the RNA polymerase, a peptide showing 30% of identity with FAH 11-20. Results indicated that MHV-infection triggers at least three distinct Ab populations: anti-MHV, anti-FAH and cross-reacting Ab. This cross-reaction implies either sequential or conformational epitopes from both the viral proteins and the autoAg and may differ between individuals.
Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Junín 956, 1113 Buenos Aires, Argentina.
Patricia A
PA
Mathieu
Karina A
KA
Gómez
Jean-Paul
JP
Coutelier
Lilia A
LA
Retegui
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000737:chemistry* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology / Q000821:virology; D015551:Autoimmunity; D001667:Binding, Competitive; D003429:Cross Reactions / Q000276:immunology; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry / Q000276:immunology; D005260:Female; D006867:Hydrolases / Q000737:chemistry / Q000276:immunology; D008099:Liver / Q000201:enzymology; D051379:Mice; D008815:Mice, Inbred Strains; D006517:Murine hepatitis virus / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein
D000914:Antibodies, Viral; D000956:Antigens, Viral; D001323:Autoantibodies; D001324:Autoantigens; D012321:DNA-Directed RNA Polymerases; D006867:Hydrolases; C020156:fumarylacetoacetase