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.

中文翻译：

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由小鼠肝炎病毒（MHV-A59）感染引起的自身免疫反应受肝色氨酸2,3-二加氧酶（TDO）调节。

在先前的工作中，我们证明了甲基色氨酸（MT）对小鼠吲哚胺2,3-二加氧酶（IDO）的抑制作用加剧了小鼠肝炎病毒（MHV-A59）感染的病理作用，表明色氨酸（TRP）分解代谢与病毒有关效果。由于第二种酶可以将TRP加氧，色氨酸2，3-二加氧酶（TDO）主要位于肝脏，因此我们决定研究其在MHV感染模型中的作用。结果表明，LM10是3-（2-（吡啶基）乙烯基）吲哚的衍生物在体内的TDO抑制作用，导致病毒感染引起的抗MHV Ab滴度降低。此外，观察到某些警报蛋白释放减少，即尿酸和高迁移率族box1蛋白（HMGB1）。因此，由于警报蛋白的释放与针对富马酰乙酰乙酸水解酶（FAH）的自身抗体（autoAb）的表达有关，因此这些autoAb也有所减少。而且，PCR结果表明TDO抑制没有消除病毒复制。此外，组织学肝脏检查未发现明显的病理，而对照和经LM10处理的MHV感染小鼠的小鼠存活率为100％。这项工作中提供的数据表明，尽管已经描述了各种TDO作用，但是特定的TDO阻断作用也可以抑制某些MHV作用，主要是抑制自身免疫反应。这样的结果应促使对各种病毒进行进一步的实验，以确认可能使用TDO抑制剂（如LM-10）来治疗病毒感染或什至是由病毒感染引发的自身免疫性疾病。