Thogoto virus infection induces sustained type I interferon responses that depend on RIG-I-like helicase signaling of conventional dendritic cells.

2.50
Hdl Handle:
http://hdl.handle.net/10033/134189
Title:
Thogoto virus infection induces sustained type I interferon responses that depend on RIG-I-like helicase signaling of conventional dendritic cells.
Authors:
Kochs, Georg; Bauer, Stefanie; Vogt, Carola; Frenz, Theresa; Tschopp, Jürg; Kalinke, Ulrich ( 0000-0003-0503-9564 ) ; Waibler, Zoe
Abstract:
Type I interferon (IFN-α/β) induction upon viral infection contributes to the early antiviral host defense and ensures survival until the onset of adaptive immunity. Many viral infections lead to an acute, transient IFN expression which peaks a few hours after infection and reverts to initial levels after 24 to 36 h. Robust IFN expression often is conferred by specialized plasmacytoid dendritic cells (pDC) and may depend on positive-feedback amplification via the type I IFN receptor (IFNAR). Here, we show that mice infected with Thogoto virus (THOV), which is an influenza virus-like orthomyxovirus transmitted by ticks, mounted sustained IFN responses that persisted up to 72 h after infection. For this purpose, we used a variant of THOV lacking its IFN-antagonistic protein ML, an elongated version of the matrix (M) protein [THOV(ΔML)]. Of note, large amounts of type I IFN were also found in the serum of mice lacking the IFNAR. Early IFN-α expression seemed to depend on Toll-like receptor (TLR) signaling, whereas prolonged IFN-α responses strictly depended on RIG-I-like helicase (RLH) signaling. Unexpectedly, THOV(ΔML)-infected bone marrow-derived pDC (BM-pDC) produced only moderate IFN levels, whereas myeloid DC (BM-mDC) showed massive IFN induction that was IPS-1-dependent, suggesting that BM-mDC are involved in the massive, sustained IFN production in THOV(ΔML)-infected animals. Thus, our data are compatible with the model that THOV(ΔML) infection is sensed in the acute phase via TLR and RLH systems, whereas at later time points only RLH signaling is responsible for the induction of sustained IFN responses.
Affiliation:
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, Freiburg, Germany.
Citation:
Thogoto virus infection induces sustained type I interferon responses that depend on RIG-I-like helicase signaling of conventional dendritic cells. 2010, 84 (23):12344-50 J. Virol.
Journal:
Journal of virology
Issue Date:
Dec-2010
URI:
http://hdl.handle.net/10033/134189
DOI:
10.1128/JVI.00931-10
PubMed ID:
20861272
Type:
Article
Language:
en
ISSN:
1098-5514
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorKochs, Georgen
dc.contributor.authorBauer, Stefanieen
dc.contributor.authorVogt, Carolaen
dc.contributor.authorFrenz, Theresaen
dc.contributor.authorTschopp, Jürgen
dc.contributor.authorKalinke, Ulrichen
dc.contributor.authorWaibler, Zoeen
dc.date.accessioned2011-06-22T14:11:44Zen
dc.date.available2011-06-22T14:11:44Zen
dc.date.issued2010-12en
dc.identifier.citationThogoto virus infection induces sustained type I interferon responses that depend on RIG-I-like helicase signaling of conventional dendritic cells. 2010, 84 (23):12344-50 J. Virol.en
dc.identifier.issn1098-5514en
dc.identifier.pmid20861272en
dc.identifier.doi10.1128/JVI.00931-10en
dc.identifier.urihttp://hdl.handle.net/10033/134189en
dc.description.abstractType I interferon (IFN-α/β) induction upon viral infection contributes to the early antiviral host defense and ensures survival until the onset of adaptive immunity. Many viral infections lead to an acute, transient IFN expression which peaks a few hours after infection and reverts to initial levels after 24 to 36 h. Robust IFN expression often is conferred by specialized plasmacytoid dendritic cells (pDC) and may depend on positive-feedback amplification via the type I IFN receptor (IFNAR). Here, we show that mice infected with Thogoto virus (THOV), which is an influenza virus-like orthomyxovirus transmitted by ticks, mounted sustained IFN responses that persisted up to 72 h after infection. For this purpose, we used a variant of THOV lacking its IFN-antagonistic protein ML, an elongated version of the matrix (M) protein [THOV(ΔML)]. Of note, large amounts of type I IFN were also found in the serum of mice lacking the IFNAR. Early IFN-α expression seemed to depend on Toll-like receptor (TLR) signaling, whereas prolonged IFN-α responses strictly depended on RIG-I-like helicase (RLH) signaling. Unexpectedly, THOV(ΔML)-infected bone marrow-derived pDC (BM-pDC) produced only moderate IFN levels, whereas myeloid DC (BM-mDC) showed massive IFN induction that was IPS-1-dependent, suggesting that BM-mDC are involved in the massive, sustained IFN production in THOV(ΔML)-infected animals. Thus, our data are compatible with the model that THOV(ΔML) infection is sensed in the acute phase via TLR and RLH systems, whereas at later time points only RLH signaling is responsible for the induction of sustained IFN responses.en
dc.language.isoenen
dc.subject.meshAdaptor Proteins, Signal Transducingen
dc.subject.meshAdaptor Proteins, Vesicular Transporten
dc.subject.meshAnimalsen
dc.subject.meshDEAD-box RNA Helicasesen
dc.subject.meshDendritic Cellsen
dc.subject.meshInterferon Type Ien
dc.subject.meshMiceen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshMice, Knockouten
dc.subject.meshModels, Immunologicalen
dc.subject.meshMyeloid Differentiation Factor 88en
dc.subject.meshOrthomyxoviridae Infectionsen
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen
dc.subject.meshSignal Transductionen
dc.subject.meshThogotovirusen
dc.titleThogoto virus infection induces sustained type I interferon responses that depend on RIG-I-like helicase signaling of conventional dendritic cells.en
dc.typeArticleen
dc.contributor.departmentAbteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, Freiburg, Germany.en
dc.identifier.journalJournal of virologyen

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