THE AUTOIMMUNE RESPONSE ELICITED BY MOUSE HEPATITIS VIRUS (MHV-A59) INFECTION IS MODULATED BY LIVER TRYPTOPHAN-2,3-DIOXYGENASE (TDO), 2019, Vega et al

Andy · Nov 15, 2019

In mice.

Highlights

• LM10 inhibit tryptophan-2,3-dioxygenase (TDO) activity after MHV-infection.
• TDO inhibition decreased anti- MHV Ab.
• Treatment produced a reduction of uric acid and HMGB1 release.
• TDO inhibition lowered the expression of autoAb against liver FAH.

Abstract
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.
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Paywall, https://www.sciencedirect.com/science/article/abs/pii/S0165247819302688
Not available via Scihub at time of posting.

@mariovitali , you might be interested in this.

mariovitali · Nov 15, 2019

@Andy Thank you. As shown below, HMGB1 which is mentioned in the paper has been previously identified as a potential research target :

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THE AUTOIMMUNE RESPONSE ELICITED BY MOUSE HEPATITIS VIRUS (MHV-A59) INFECTION IS MODULATED BY LIVER TRYPTOPHAN-2,3-DIOXYGENASE (TDO), 2019, Vega et al

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THE AUTOIMMUNE RESPONSE ELICITED BY MOUSE HEPATITIS VIRUS (MHV-A59) INFECTION IS MODULATED BY LIVER TRYPTOPHAN-2,3-DIOXYGENASE (TDO), 2019, Vega et al

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