title: Antiviral Effect of IDO in Mouse Fibroblast Cells During Influenza Virus Infection.
abstract: While upregulation of 2,3-dioxygenase (IDO) accompanied by degradation of tryptophan along the kynurenine pathway have been reported to exert antimicrobial effects against a wide range of infectious agents, its role in the replication of influenza A virus remains uncertain. We performed experiments using influenza A/WSN/33 virus infection of mouse fibroblast cell-line (NIH-3T3) to study the effects of IDO on viral replication. Influenza infection resulted in prominent elevations of transcripts encoding IDO, interferon (IFN)-β, and segment 8 of the virus in NIH-3T3 cells. Introduction of siRNA targeted against IDO followed by infection resulted in further increased levels of viral RNA without altering IFN-β expression. Inhibition of IDO during the infection also resulted in reduction of virus-driven upregulation of 3-hydroxyanthranilate 3,4-dioxygenase (HAAO), but not kynurenine 3-monooxygenase (KMO), which are enzymes downstream in the kynurenine pathway. Thus, induction of IDO appears to contribute to limiting replication of the WSN/33 strain of influenza A virus in murine NIH-3T3 cells.
authors.affiliation: 1 Department of Anatomy, Histology and Embryology, Changsha Medical University , Changsha, China .|2 Department of Neuroscience, Karolinska Institutet , Stockholm, Sweden .
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: 2 Department of Neuroscience, Karolinska Institutet , Stockholm, Sweden .
authors.forename: Håkan
authors.initials: H
authors.lastname: Karlsson
mesh_terms: D050561:3-Hydroxyanthranilate 3,4-Dioxygenase / Q000235:genetics; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral; D055785:Gene Knockdown Techniques; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology; D016899:Interferon-beta / Q000235:genetics; D051379:Mice; D041681:NIH 3T3 Cells; D009976:Orthomyxoviridae Infections / Q000201:enzymology* / Q000821:virology; D014364:Tryptophan / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D014764:Viral Proteins; D016899:Interferon-beta; D014364:Tryptophan; D050561:3-Hydroxyanthranilate 3,4-Dioxygenase
keywords: 2,3-dioxygenase; antiviral effect; influenza A/WSN/33 virus