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

Details

Serval ID
serval:BIB_32E657FF10EB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Thogoto virus infection induces sustained type I interferon responses that depend on RIG-I-like helicase signaling of conventional dendritic cells.
Journal
Journal of Virology
Author(s)
Kochs G., Bauer S., Vogt C., Frenz T., Tschopp J., Kalinke U., Waibler Z.
ISSN
1098-5514[electronic], 0022-538X[linking]
Publication state
Published
Issued date
2010
Peer-reviewed
Oui
Volume
84
Number
23
Pages
12344-12350
Language
english
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.
Keywords
VACCINIA VIRUS, ML PROTEIN, TRANSCRIPTION FACTOR, GENE-PRODUCT, IFN-ALPHA, MICE, INDUCTION, DEFENSE, MYD88, ORTHOMYXOVIRUS
Pubmed
Web of science
Open Access
Yes
Create date
26/11/2010 10:07
Last modification date
20/08/2019 13:18
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