Regulation of kynurenine biosynthesis during influenza virus infection

Lana Gaelings, Sandra Söderholm, Andrii Bugai, Yu Fu, Jatin Nandania, Bert Schepens, Martina B. Lorey, Janne Tynell, Liesbeth Vande Ginste, Ronan Le Goffic, Matthew S. Miller, Marika Kuisma, Varpu Marjomäki, Jef De Brabander, Sampsa Matikainen, Tuula A. Nyman, Dennis H. Bamford, Xavier Saelens, Ilkka Julkunen, Henrik PaavilainenVeijo Hukkanen, Vidya Velagapudi, Denis E. Kainov

Research output: Contribution to journalEditorial

14 Scopus citations

Abstract

Influenza A viruses (IAVs) 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 (IFNs), which upregulated production of indoleamine-2,3-dioxygenase (IDO1), which catalysed the kynurenine biosynthesis. Furthermore, IAV attenuated the IDO1 expression and the production of kynurenine through its NS1 protein. Interestingly, inhibition of viral replication prior to IFN induction limited IDO1 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.

Original languageEnglish (US)
Pages (from-to)222-236
Number of pages15
JournalFEBS Journal
Volume284
Issue number2
DOIs
StatePublished - Jan 1 2017

Keywords

  • host–pathogen interaction
  • indoleamine-pyrrole 2,3-dioxygenase (IDO1)
  • influenza virus
  • innate immunity
  • interferon

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Gaelings, L., Söderholm, S., Bugai, A., Fu, Y., Nandania, J., Schepens, B., Lorey, M. B., Tynell, J., Vande Ginste, L., Le Goffic, R., Miller, M. S., Kuisma, M., Marjomäki, V., De Brabander, J., Matikainen, S., Nyman, T. A., Bamford, D. H., Saelens, X., Julkunen, I., ... Kainov, D. E. (2017). Regulation of kynurenine biosynthesis during influenza virus infection. FEBS Journal, 284(2), 222-236. https://doi.org/10.1111/febs.13966