The autoimmune response elicited by mouse hepatitis virus (MHV-A59) infection is modulated by liver tryptophan-2,3-dioxygenase (TDO).

Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 7910006 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0542 (Electronic) Linking ISSN: 01652478 NLM ISO Abbreviation: Immunol Lett Subsets: MEDLINE

Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press.

Autoimmune Diseases/*enzymology ; Autoimmunity/*drug effects ; Coronavirus Infections/*enzymology ; Coronavirus Infections/*immunology ; Liver/*enzymology ; Murine hepatitis virus/*immunology ; Tryptophan Oxygenase/*antagonists & inhibitors ; Tryptophan Oxygenase/*metabolism; Alarmins/metabolism ; Animals ; Autoantibodies/drug effects ; Autoantibodies/immunology ; Autoimmune Diseases/drug therapy ; Autoimmune Diseases/immunology ; Autoimmune Diseases/virology ; Coronavirus Infections/drug therapy ; Coronavirus Infections/virology ; Female ; HMGB1 Protein/blood ; HMGB1 Protein/metabolism ; Hydrolases/immunology ; Indoles/therapeutic use ; Liver/drug effects ; Liver/immunology ; Liver/pathology ; Mice ; Mice, Inbred BALB C ; Murine hepatitis virus/drug effects ; Murine hepatitis virus/growth & development ; Tryptophan/metabolism ; Tryptophan Oxygenase/genetics ; Uric Acid/blood ; Uric Acid/metabolism ; Virus Replication/drug effects ; Virus Replication/immunology

In a previous work we demonstrated that inhibition of mouse indoleamine 2,3-dioxygenase (IDO) by methyltryptophan (MT) exacerbated the pathological actions of mouse hepatitis virus (MHV-A59) infection, suggesting that tryptophan (TRP) catabolism was involved in viral effects. Since there is a second enzyme that dioxygenates TRP, tryptophan-2, 3-dioxygenase (TDO), which is mainly located in liver, we decided to study its role in our model of MHV-infection. Results showed that in vivo TDO inhibition by LM10, a derivative of 3-(2-(pyridyl) ethenyl) indole, resulted in a decrease of anti- MHV Ab titers induced by the virus infection. Besides, a reduction of some alarmin release, i.e, uric acid and high-mobility group box1 protein (HMGB1), was observed. Accordingly, since alarmin liberation was related to the expression of autoantibodies (autoAb) to fumarylacetoacetate hydrolase (FAH), these autoAb also diminished. Moreover, PCR results indicated that TDO inhibition did not abolish viral replication. Furthermore, histological liver examination did not reveal strong pathologies, whereas mouse survival was hundred percent in control as well as in MHV-infected mice treated with LM10. Data presented in this work indicate that in spite of the various TDO actions already described, specific TDO blockage could also restrain some MHV actions, mainly suppressing autoimmune reactions. Such results should prompt further experiments with various viruses to confirm the possible use of a TDO inhibitor such as LM-10 to treat either viral infections or even autoimmune diseases triggered by a viral infection.
(Copyright © 2019 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Keywords: Autoantibodies; HMGB1; Mouse hepatitis virus; Tryptophan-2,3-dioxygenase; Uric acid

0 (Alarmins)
0 (Autoantibodies)
0 (HMGB1 Protein)
0 (HMGB1 protein, mouse)
0 (Indoles)
0 (TDO inhibitor LM10)
268B43MJ25 (Uric Acid)
8DUH1N11BX (Tryptophan)
EC 1.13.11.11 (Tryptophan Oxygenase)
EC 3.- (Hydrolases)
EC 3.7.1.2 (fumarylacetoacetase)

Date Created: 20191115 Date Completed: 20201023 Latest Revision: 20201116

20231215

10.1016/j.imlet.2019.11.004

31726186