title: The autoimmune response induced by mouse hepatitis virus A59 is expanded by a hepatotoxic agent.
abstract: Mouse hepatitis virus strain A59 (MHV-A59) triggers various pathologies in several mouse strains, including hypergammaglobulinaemia, hepatitis and thymus involution. We reported previously the presence of autoantibodies (autoAb) to liver and kidney fumarylacetoacetate hydrolase (FAH) in sera from mice infected with MHV-A59. Long-term MHV-infected mice represented a good model of non-pathogenic autoimmune response since the animals were apparently healthy in spite of the presence of autoAb. The aim of this work was to see whether a severe liver injury, which releases endogenous adjuvants, i.e. danger signals, could elicit a broader spectrum of autoAb and perhaps signs of autoimmune hepatitis. Carbon tetrachloride (CCl(4)) was injected into mice 30 days after MHV infection, and serum was assayed for autoAb and total IgG 20 days later. The association of MHV infection with the toxic effects of CCl(4) resulted in hypergammaglobulinaemia and the production of autoAb to various liver and kidney proteins. Histological examination of liver samples showed tissue damages but without significant differences between the animals submitted to MHV+CCl(4) and controls, which were either infected by MHV without CCl(4), or poisoned by CCl(4) in the absence of MHV infection. Those results show that liver injury after viral infection may lead to the spreading of the immune response and to an increase of serum IgG, suggesting that the procedure used herein could simulate the onset of autoimmune hepatitis.
authors.affiliation: Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Junín 956, Buenos Aires, Argentina.
authors.forename: José L
authors.initials: JL
authors.lastname: Aparicio
authors.forename: Maite
authors.initials: M
authors.lastname: Duhalde-Vega
authors.forename: María E
authors.initials: ME
authors.lastname: Loureiro
authors.forename: Lilia A
authors.initials: LA
authors.lastname: Retegui
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity; D002251:Carbon Tetrachloride / Q000633:toxicity*; D005260:Female; D019693:Hepatitis, Autoimmune / Q000209:etiology; D006524:Hepatitis, Viral, Animal / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D006867:Hydrolases / Q000276:immunology; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008099:Liver / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D006517:Murine hepatitis virus / Q000276:immunology*; D009928:Organ Specificity
chemical_list: D001323:Autoantibodies; D002251:Carbon Tetrachloride; D006867:Hydrolases; C020156:fumarylacetoacetase