Regulation of kynurenine biosynthesis during influenza virus infection

Lana Gaelings, Sandra Linnea Söderholm, Andrii Bugai, Yu Fu, Jatin Nandania, Bert Schepens, Martina B. Lorey, Janne Tynell, Varpu Marjomäki, Sampsa Matikainen, Tuula Anneli Nyman, Xavier Saelens, I. Julkunen, Vidya Velagapudi, Denis Kainov

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Kuvaus

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.
Alkuperäiskielienglanti
LehtiThe FEBS Journal
Vuosikerta284
Numero2
Sivut222-236
Sivumäärä15
ISSN1742-464X
DOI - pysyväislinkit
TilaJulkaistu - tammikuuta 2017
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 318 Lääketieteen bioteknologia

Lainaa tätä

Gaelings, Lana ; Söderholm, Sandra Linnea ; Bugai, Andrii ; Fu, Yu ; Nandania, Jatin ; Schepens, Bert ; Lorey, Martina B. ; Tynell, Janne ; Marjomäki, Varpu ; Matikainen, Sampsa ; Nyman, Tuula Anneli ; Saelens, Xavier ; Julkunen, I. ; Velagapudi, Vidya ; Kainov, Denis. / Regulation of kynurenine biosynthesis during influenza virus infection. Julkaisussa: The FEBS Journal. 2017 ; Vuosikerta 284, Nro 2. Sivut 222-236.
@article{8eeb189bcf664e55aca37731a4065d82,
title = "Regulation of kynurenine biosynthesis during influenza virus infection",
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 = "318 Medical biotechnology",
author = "Lana Gaelings and S{\"o}derholm, {Sandra Linnea} and Andrii Bugai and Yu Fu and Jatin Nandania and Bert Schepens and Lorey, {Martina B.} and Janne Tynell and Varpu Marjom{\"a}ki and Sampsa Matikainen and Nyman, {Tuula Anneli} and Xavier Saelens and I. Julkunen and Vidya Velagapudi and Denis Kainov",
year = "2017",
month = "1",
doi = "10.1111/febs.13966",
language = "English",
volume = "284",
pages = "222--236",
journal = "The FEBS Journal",
issn = "1742-464X",
publisher = "Wiley-Blackwell Publishing Asia",
number = "2",

}

Gaelings, L, Söderholm, SL, Bugai, A, Fu, Y, Nandania, J, Schepens, B, Lorey, MB, Tynell, J, Marjomäki, V, Matikainen, S, Nyman, TA, Saelens, X, Julkunen, I, Velagapudi, V & Kainov, D 2017, 'Regulation of kynurenine biosynthesis during influenza virus infection', The FEBS Journal, Vuosikerta 284, Nro 2, Sivut 222-236. https://doi.org/10.1111/febs.13966

Regulation of kynurenine biosynthesis during influenza virus infection. / Gaelings, Lana; Söderholm, Sandra Linnea; Bugai, Andrii; Fu, Yu; Nandania, Jatin; Schepens, Bert; Lorey, Martina B.; Tynell, Janne; Marjomäki, Varpu; Matikainen, Sampsa; Nyman, Tuula Anneli; Saelens, Xavier; Julkunen, I.; Velagapudi, Vidya; Kainov, Denis.

julkaisussa: The FEBS Journal, Vuosikerta 284, Nro 2, 01.2017, s. 222-236.

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

TY - JOUR

T1 - Regulation of kynurenine biosynthesis during influenza virus infection

AU - Gaelings, Lana

AU - Söderholm, Sandra Linnea

AU - Bugai, Andrii

AU - Fu, Yu

AU - Nandania, Jatin

AU - Schepens, Bert

AU - Lorey, Martina B.

AU - Tynell, Janne

AU - Marjomäki, Varpu

AU - Matikainen, Sampsa

AU - Nyman, Tuula Anneli

AU - Saelens, Xavier

AU - Julkunen, I.

AU - Velagapudi, Vidya

AU - Kainov, Denis

PY - 2017/1

Y1 - 2017/1

N2 - 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.

AB - 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.

KW - 318 Medical biotechnology

U2 - 10.1111/febs.13966

DO - 10.1111/febs.13966

M3 - Article

VL - 284

SP - 222

EP - 236

JO - The FEBS Journal

JF - The FEBS Journal

SN - 1742-464X

IS - 2

ER -