title: 5-Hydroxytryptophan, a major product of tryptophan degradation, is essential for optimal replication of human parainfluenza virus.
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.
authors.affiliation: 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.
authors.forename: M A G
authors.initials: MAG
authors.lastname: Rabbani
authors.affiliation: 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.
authors.forename: Sailen
authors.initials: S
authors.lastname: Barik
mesh_terms: D006916:5-Hydroxytryptophan / Q000378:metabolism* / Q000494:pharmacology; D000072283:A549 Cells; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000494:pharmacology*; D007372:Interferons / Q000494:pharmacology; D007737:Kynurenine / Q000378:metabolism; D008253:Macaca mulatta; D010224:Parainfluenza Virus 3, Human / Q000254:growth & development* / Q000378:metabolism; D010253:Respirovirus Infections / Q000188:drug therapy; D014364:Tryptophan / Q000737:chemistry / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects* / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D014364:Tryptophan; D007372:Interferons; D006916:5-Hydroxytryptophan
keywords: 5-HTP; IDO; ISG; Kynurenine; Melatonin; Parainfluenza virus; Paramyxovirus; Serotonin; Tryptophan