title: Levo-1-methyl tryptophan aggravates the effects of mouse hepatitis virus (MHV-A59) infection.
abstract: Mice infected with mouse hepatitis virus A59 (MHV-A59) develop autoantibodies (autoAb) to liver and kidney fumarylacetoacetate hydrolase (FAH) with a concomitant enhancement of transaminases and release of alarmins such as uric acid and high-mobility group box protein 1 (HMGB1). Tryptophan catabolism is an endogenous mechanism that restricts excessive immune responses, thereby preventing immunopathology. Since indoleamine-2,3-dioxygenase (IDO) is the key and rate-limiting enzyme of tryptophan catabolism, the aim of this work was to explore whether specific inhibition of IDO by Levo-1-methyl tryptophan (MT) could affect MHV actions. Results showed that MT strongly enhanced the hypergammaglobulinemia induced by the virus, as well as anti-MHV Ab and uric acid release. Moreover, infected mice treated with MT did express anti-FAH autoAb and high levels of serum HMGB1. Survival of MHV-infected animals treated with MT was severely reduced compared with that of MHV-infected mice or controls only treated with MT. Furthermore, histological liver examination indicated that MT induced fibrosis in MHV-infected animals, whereas MT itself increased uric acid levels without shortening the animal life Thus, under our experimental conditions, results indicated an exacerbated response to MHV infection when IDO was blocked by MT.
authors.affiliation: Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina.
authors.forename: Maite
authors.initials: M
authors.lastname: Duhalde Vega
authors.affiliation: Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina.
authors.forename: José L
authors.initials: JL
authors.lastname: Aparício
authors.affiliation: Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina. Electronic address: lretegui@retina.ar.
authors.forename: Lilia A
authors.initials: LA
authors.lastname: Retegui
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001323:Autoantibodies / Q000276:immunology; D002460:Cell Line; D018352:Coronavirus Infections / Q000097:blood / Q000276:immunology / Q000473:pathology; D005260:Female; D024243:HMGB1 Protein / Q000097:blood; D006524:Hepatitis, Viral, Animal / Q000097:blood / Q000276:immunology / Q000473:pathology; D006867:Hydrolases / Q000276:immunology; D006942:Hypergammaglobulinemia / Q000097:blood / Q000276:immunology / Q000473:pathology; D007136:Immunoglobulins / Q000097:blood; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors; D007668:Kidney / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008807:Mice, Inbred BALB C; D006517:Murine hepatitis virus / Q000276:immunology; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000494:pharmacology; D014527:Uric Acid / Q000097:blood
chemical_list: D000914:Antibodies, Viral; D001323:Autoantibodies; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D007136:Immunoglobulins; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D014527:Uric Acid; C028129:tryptophan methyl ester; D014364:Tryptophan; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D006867:Hydrolases; C020156:fumarylacetoacetase
keywords: HMGB1; Indoleamine-2,3-dioxygenase; Levo-1-methyl tryptophan; Mouse hepatitis virus; Uric acid