Interferon regulatory factor-1 protects from fatal neurotropic infection with vesicular stomatitis virus by specific inhibition of viral replication in neurons.

2.50
Hdl Handle:
http://hdl.handle.net/10033/315240
Title:
Interferon regulatory factor-1 protects from fatal neurotropic infection with vesicular stomatitis virus by specific inhibition of viral replication in neurons.
Authors:
Nair, Sharmila; Michaelsen-Preusse, Kristin; Finsterbusch, Katja; Stegemann-Koniszewski, Sabine; Bruder, Dunja ( 0000-0003-3066-189X ) ; Grashoff, Martina; Korte, Martin; Köster, Mario; Kalinke, Ulrich ( 0000-0003-0503-9564 ) ; Hauser, Hansjörg; Kröger, Andrea ( 0000-0002-3131-6580 )
Abstract:
The innate immune system protects cells against invading viral pathogens by the auto- and paracrine action of type I interferon (IFN). In addition, the interferon regulatory factor (IRF)-1 can induce alternative intrinsic antiviral responses. Although both, type I IFN and IRF-1 mediate their antiviral action by inducing overlapping subsets of IFN stimulated genes, the functional role of this alternative antiviral action of IRF-1 in context of viral infections in vivo remains unknown. Here, we report that IRF-1 is essential to counteract the neuropathology of vesicular stomatitis virus (VSV). IFN- and IRF-1-dependent antiviral responses act sequentially to create a layered antiviral protection program against VSV infections. Upon intranasal infection, VSV is cleared in the presence or absence of IRF-1 in peripheral organs, but IRF-1-/- mice continue to propagate the virus in the brain and succumb. Although rapid IFN induction leads to a decline in VSV titers early on, viral replication is re-enforced in the brains of IRF-1-/- mice. While IFN provides short-term protection, IRF-1 is induced with delayed kinetics and controls viral replication at later stages of infection. IRF-1 has no influence on viral entry but inhibits viral replication in neurons and viral spread through the CNS, which leads to fatal inflammatory responses in the CNS. These data support a temporal, non-redundant antiviral function of type I IFN and IRF-1, the latter playing a crucial role in late time points of VSV infection in the brain.
Affiliation:
Research Group Innate Immunity and Infection, Helmholtz Centre for Infection Research, Braunschweig, Germany
Citation:
Interferon regulatory factor-1 protects from fatal neurotropic infection with vesicular stomatitis virus by specific inhibition of viral replication in neurons. 2014, 10 (3):e1003999 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
Mar-2014
URI:
http://hdl.handle.net/10033/315240
DOI:
10.1371/journal.ppat.1003999
PubMed ID:
24675692
Type:
Article
Language:
en
ISSN:
1553-7374
Appears in Collections:
publications of the research group intravital microscopy in infection and immunity (INMI)

Full metadata record

DC FieldValue Language
dc.contributor.authorNair, Sharmilaen
dc.contributor.authorMichaelsen-Preusse, Kristinen
dc.contributor.authorFinsterbusch, Katjaen
dc.contributor.authorStegemann-Koniszewski, Sabineen
dc.contributor.authorBruder, Dunjaen
dc.contributor.authorGrashoff, Martinaen
dc.contributor.authorKorte, Martinen
dc.contributor.authorKöster, Marioen
dc.contributor.authorKalinke, Ulrichen
dc.contributor.authorHauser, Hansjörgen
dc.contributor.authorKröger, Andreaen
dc.date.accessioned2014-04-03T14:17:07Zen
dc.date.available2014-04-03T14:17:07Zen
dc.date.issued2014-03en
dc.identifier.citationInterferon regulatory factor-1 protects from fatal neurotropic infection with vesicular stomatitis virus by specific inhibition of viral replication in neurons. 2014, 10 (3):e1003999 PLoS Pathog.en
dc.identifier.issn1553-7374en
dc.identifier.pmid24675692en
dc.identifier.doi10.1371/journal.ppat.1003999en
dc.identifier.urihttp://hdl.handle.net/10033/315240en
dc.description.abstractThe innate immune system protects cells against invading viral pathogens by the auto- and paracrine action of type I interferon (IFN). In addition, the interferon regulatory factor (IRF)-1 can induce alternative intrinsic antiviral responses. Although both, type I IFN and IRF-1 mediate their antiviral action by inducing overlapping subsets of IFN stimulated genes, the functional role of this alternative antiviral action of IRF-1 in context of viral infections in vivo remains unknown. Here, we report that IRF-1 is essential to counteract the neuropathology of vesicular stomatitis virus (VSV). IFN- and IRF-1-dependent antiviral responses act sequentially to create a layered antiviral protection program against VSV infections. Upon intranasal infection, VSV is cleared in the presence or absence of IRF-1 in peripheral organs, but IRF-1-/- mice continue to propagate the virus in the brain and succumb. Although rapid IFN induction leads to a decline in VSV titers early on, viral replication is re-enforced in the brains of IRF-1-/- mice. While IFN provides short-term protection, IRF-1 is induced with delayed kinetics and controls viral replication at later stages of infection. IRF-1 has no influence on viral entry but inhibits viral replication in neurons and viral spread through the CNS, which leads to fatal inflammatory responses in the CNS. These data support a temporal, non-redundant antiviral function of type I IFN and IRF-1, the latter playing a crucial role in late time points of VSV infection in the brain.en
dc.language.isoenen
dc.rightsArchived with thanks to PLoS pathogensen
dc.titleInterferon regulatory factor-1 protects from fatal neurotropic infection with vesicular stomatitis virus by specific inhibition of viral replication in neurons.en
dc.typeArticleen
dc.contributor.departmentResearch Group Innate Immunity and Infection, Helmholtz Centre for Infection Research, Braunschweig, Germanyen
dc.identifier.journalPLoS pathogensen

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