tetano
Editor, Senior Moderator
FEBS J. 2016 Nov 18. doi: 10.1111/febs.13966. [Epub ahead of print]
[h=1]Regulation of Kynurenine Biosynthesis during Influenza Virus Infection.[/h] Gaelings L[SUP]1[/SUP], S?derholm S[SUP]2,[/SUP][SUP]3[/SUP], Bugai A[SUP]4[/SUP], Fu Y[SUP]1[/SUP], Nandania J[SUP]1[/SUP], Schepens B[SUP]5,[/SUP][SUP]6[/SUP], Lorey MB[SUP]3[/SUP], Tynell J[SUP]7[/SUP], Vande Ginste L[SUP]4,[/SUP][SUP]5[/SUP], Le Goffic R[SUP]8[/SUP], Miller MS[SUP]9[/SUP], Kuisma M[SUP]4[/SUP], Marjom?ki V[SUP]10[/SUP], De Brabander J[SUP]11[/SUP], Matikainen S[SUP]3[/SUP], Nyman TA[SUP]12[/SUP], Bamford D[SUP]2[/SUP], Saelens X[SUP]4,[/SUP][SUP]5[/SUP], Julkunen I[SUP]7,[/SUP][SUP]13[/SUP], Paavilainen H[SUP]13[/SUP], Hukkanen V[SUP]13[/SUP], Velagapudi V[SUP]1[/SUP], Kainov DE[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[h=4]KEYWORDS:[/h] 3-dioxygenase (IDO1); host-pathogen interaction; indoleamine-pyrrole 2; influenza virus; innate immunity; interferon
PMID: 27860276 DOI: 10.1111/febs.13966
[PubMed - as supplied by publisher]
[h=1]Regulation of Kynurenine Biosynthesis during Influenza Virus Infection.[/h] Gaelings L[SUP]1[/SUP], S?derholm S[SUP]2,[/SUP][SUP]3[/SUP], Bugai A[SUP]4[/SUP], Fu Y[SUP]1[/SUP], Nandania J[SUP]1[/SUP], Schepens B[SUP]5,[/SUP][SUP]6[/SUP], Lorey MB[SUP]3[/SUP], Tynell J[SUP]7[/SUP], Vande Ginste L[SUP]4,[/SUP][SUP]5[/SUP], Le Goffic R[SUP]8[/SUP], Miller MS[SUP]9[/SUP], Kuisma M[SUP]4[/SUP], Marjom?ki V[SUP]10[/SUP], De Brabander J[SUP]11[/SUP], Matikainen S[SUP]3[/SUP], Nyman TA[SUP]12[/SUP], Bamford D[SUP]2[/SUP], Saelens X[SUP]4,[/SUP][SUP]5[/SUP], Julkunen I[SUP]7,[/SUP][SUP]13[/SUP], Paavilainen H[SUP]13[/SUP], Hukkanen V[SUP]13[/SUP], Velagapudi V[SUP]1[/SUP], Kainov DE[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[h=4]KEYWORDS:[/h] 3-dioxygenase (IDO1); host-pathogen interaction; indoleamine-pyrrole 2; influenza virus; innate immunity; interferon
PMID: 27860276 DOI: 10.1111/febs.13966
[PubMed - as supplied by publisher]