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Regulation of kynurenine biosynthesis during influenza virus infection
Author(s) -
Gaelings Lana,
Söderholm Sandra,
Bugai Andrii,
Fu Yu,
Nandania Jatin,
Schepens Bert,
Lorey Martina B.,
Tynell Janne,
Vande Ginste Liesbeth,
Le Goffic Ronan,
Miller Matthew S.,
Kuisma Marika,
Marjomäki Varpu,
De Brabander Jef,
Matikainen Sampsa,
Nyman Tuula A.,
Bamford Dennis H.,
Saelens Xavier,
Julkunen Ilkka,
Paavilainen Henrik,
Hukkanen Veijo,
Velagapudi Vidya,
Kainov Denis E.
Publication year - 2017
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13966
Subject(s) - virology , biosynthesis , kynurenine , virus , kynurenine pathway , influenza a virus , biology , microbiology and biotechnology , gene , tryptophan , biochemistry , amino acid
Influenza A viruses ( IAV s) remain serious threats to public health because of the shortage of effective means of control. Developing more effective virus control modalities requires better understanding of virus–host interactions. It has previously been shown that IAV induces the production of kynurenine, which suppresses T‐cell responses, enhances pain hypersensitivity and disturbs behaviour in infected animals. However, the regulation of kynurenine biosynthesis during IAV infection remains elusive. Here we showed that IAV infection induced expression of interferons ( IFN s ), which upregulated production of indoleamine‐2,3‐dioxygenase ( IDO 1), which catalysed the kynurenine biosynthesis. Furthermore, IAV attenuated the IDO 1 expression and the production of kynurenine through its NS 1 protein. Interestingly, inhibition of viral replication prior to IFN induction limited IDO 1 expression, while inhibition after did not. Finally, we showed that kynurenine biosynthesis was activated in macrophages in response to other stimuli, such as influenza B virus, herpes simplex virus 1 and 2 as well as bacterial lipopolysaccharides. Thus, the tight regulation of the kynurenine biosynthesis by host cell and, perhaps, pathogen might be a basic signature of a wide range of host–pathogen interactions, which should be taken into account during development of novel antiviral and antibacterial drugs.