Format

Send to

Choose Destination
FEBS J. 2017 Jan;284(2):222-236. doi: 10.1111/febs.13966. Epub 2016 Dec 14.

Regulation of kynurenine biosynthesis during influenza virus infection.

Author information

1
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland.
2
Institute of Biotechnology (BI), University of Helsinki, Finland.
3
Finnish Institute of Occupational Health (TTL), Helsinki, Finland.
4
Medicum, Department of Biochemistry and Developmental Biology, University of Helsinki, Finland.
5
Medical Biotechnology Center, VIB, Ghent, Belgium.
6
Department of Biomedical Molecular Biology, Ghent University, Belgium.
7
National Institute for Health and Welfare (THL), Helsinki, Finland.
8
Centre de Recherche de Jouy-en-Josas UR0892 Unité VIM - Virologie & Immunologie Moléculaires, Domaine de Vilvert, Jouy-en-Josas, France.
9
Department of Biochemistry and Biomedical Sciences, Institute for Infectious Diseases Research, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
10
Department of Biological and Environmental Science, Nanoscience Center, University of Jyväskylä, Finland.
11
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
12
Institute of Clinical Medicine, Rikshospitalet, Oslo, Norway.
13
Department of Virology, University of Turku, Finland.

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.

KEYWORDS:

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

PMID:
27860276
DOI:
10.1111/febs.13966
[Indexed for MEDLINE]
Free full text

Publication type, MeSH terms, Substances

Publication type

MeSH terms

Substances

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center