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Virology. 2017 Mar;503:46-51. doi: 10.1016/j.virol.2017.01.007. Epub 2017 Jan 20.

5-Hydroxytryptophan, a major product of tryptophan degradation, is essential for optimal replication of human parainfluenza virus.

Author information

1
Department of Biological, Geological and Environmental Sciences, and Center for Gene Regulation in Health and Disease, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115, United States.
2
Department of Biological, Geological and Environmental Sciences, and Center for Gene Regulation in Health and Disease, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115, United States. Electronic address: barikfamily@gmail.com.

Abstract

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.

KEYWORDS:

5-HTP; IDO; ISG; Kynurenine; Melatonin; Parainfluenza virus; Paramyxovirus; Serotonin; Tryptophan

PMID:
28113063
PMCID:
PMC5478882
DOI:
10.1016/j.virol.2017.01.007
[Indexed for MEDLINE]
Free PMC Article

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