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Regulation of kynurenine biosynthesis during influenza virus infection

(2016) FEBS JOURNAL. 284(2). p.222-236
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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, A VIRUS, INDOLEAMINE 2, 3-DIOXYGENASE, HUMAN MACROPHAGES, NS1 PROTEIN, ANTIVIRAL RESPONSES, TRYPTOPHAN CATABOLISM, EXPRESSION, CELLS, SALIPHENYLHALAMIDE, REPLICATION

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Chicago
Gaelings, Lana, Sandra Söderholm, Andrii Bugai, Yu-Kui Fu, Jatin Nandania, Bert Schepens, Martina B. Lorey, et al. 2016. “Regulation of Kynurenine Biosynthesis During Influenza Virus Infection.” Febs Journal 284 (2): 222–236.
APA
Gaelings, L., Söderholm, S., Bugai, A., Fu, Y.-K., Nandania, J., Schepens, B., Lorey, M. B., et al. (2016). Regulation of kynurenine biosynthesis during influenza virus infection. FEBS JOURNAL, 284(2), 222–236.
Vancouver
1.
Gaelings L, Söderholm S, Bugai A, Fu Y-K, Nandania J, Schepens B, et al. Regulation of kynurenine biosynthesis during influenza virus infection. FEBS JOURNAL. 2016;284(2):222–36.
MLA
Gaelings, Lana et al. “Regulation of Kynurenine Biosynthesis During Influenza Virus Infection.” FEBS JOURNAL 284.2 (2016): 222–236. Print.
@article{8512273,
  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.},
  author       = {Gaelings, Lana and Söderholm, Sandra and Bugai, Andrii and Fu, Yu-Kui and Nandania, Jatin and Schepens, Bert and Lorey, Martina B. and Tynell, Janne and Vande Ginste, Liesbeth and Le Goffic, Ronan and Miller, Matthew S. and Kuisma, Marika and Marjomäki, Varpu and De Brabander, Jef and Matikainen, Sampsa and Nyman, Tuula A. and Bamford, Dennis H. and Saelens, Xavier and Julkunen, Ilkka and Paavilainen, Henrik and Hukkanen, Veijo and Velagapudi, Vidya and Kainov, Denis E.},
  issn         = {1742-464X},
  journal      = {FEBS JOURNAL},
  keywords     = {host-pathogen interaction,indoleamine-pyrrole 2,3-dioxygenase (IDO1),influenza virus,innate immunity,interferon,A VIRUS,INDOLEAMINE 2,3-DIOXYGENASE,HUMAN MACROPHAGES,NS1 PROTEIN,ANTIVIRAL RESPONSES,TRYPTOPHAN CATABOLISM,EXPRESSION,CELLS,SALIPHENYLHALAMIDE,REPLICATION},
  language     = {eng},
  number       = {2},
  pages        = {222--236},
  title        = {Regulation of kynurenine biosynthesis during influenza virus infection},
  url          = {http://dx.doi.org/10.1111/febs.13966},
  volume       = {284},
  year         = {2016},
}

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