5-Hydroxytryptophan, a major product of tryptophan degradation, is essential for optimal replication of human parainfluenza virus.
5-Hydroxytryptophan, a major product of tryptophan degradation, is essential for optimal replication of human parainfluenza virus.
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DOI：
10.1016/j.virol.2017.01.007
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发表时间：
2017-03
期刊：
影响因子：
3.7
通讯作者：
Barik S
中科院分区：
文献类型：
--
作者：
Rabbani MAG;Barik S
干扰素 (IFN) 通过诱导一大类细胞基因（称为干扰素 (IFN) 刺激基因 (ISG)）来发挥其抗病毒作用。该家族中一个有趣的成员是吲哚胺 2,3-双加氧酶 (IDO)，它催化色氨酸 (Trp) 降解主要分支（犬尿氨酸途径）的第一步，也是限速步骤。我们最近表明，IDO 能强烈抑制人类副流感病毒 3 型 (PIV3)，这是一种重要的呼吸道病原体。在这里，我们表明，5-羟色氨酸 (5-HTP) 是色氨酸降解替代分支的第一个产物，也是血清素前体，对于保护细胞培养中的病毒生长免受 IDO 的影响至关重要。我们还表明，IDO 对 PIV3 的明显抗病毒作用并不是由于犬尿氨酸途径代谢物的产生，而是由于 IDO 消耗了细胞内 Trp，因此这种稀有氨基酸无法用于替代的前病毒 5-HTP 途径。
Interferon (IFN) exerts its antiviral effect by inducing a large family of cellular genes, named interferon (IFN)-stimulated genes (ISGs). An intriguing member of this family is indoleamine 2,3-dioxygenase (IDO), which catalyzes the first and rate-limiting step of the main branch of tryptophan (Trp) degradation, the kynurenine pathway. We recently showed that IDO strongly inhibits human parainfluenza virus type 3 (PIV3), a significant respiratory pathogen. Here, we show that 5-hydoxytryptophan (5-HTP), the first product of an alternative branch of Trp degradation and a serotonin precursor, is essential to protect virus growth against IDO in cell culture. We also show that the apparent antiviral effect of IDO on PIV3 is not due to the generation of the kynurenine pathway metabolites, but rather due to the depletion of intracellular Trp by IDO, as a result of which this rare amino acid becomes unavailable for the alternative, proviral 5-HTP pathway.