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Thogoto virus infection induces sustained type I interferon responses that depend on RIG-I-like helicase signaling of conventional dendritic cells
- Publication Year :
- 2010
-
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.
- Subjects :
- Immunology
Cellular Response to Infection
Microbiology
Virus
DEAD-box RNA Helicases
Mice
Immune system
Orthomyxoviridae Infections
Interferon
Virology
medicine
Animals
Adaptor Proteins, Signal Transducing
Mice, Knockout
biology
RIG-I
Reverse Transcriptase Polymerase Chain Reaction
Models, Immunological
Dendritic cell
Dendritic Cells
Acquired immune system
biology.organism_classification
Mice, Inbred C57BL
Adaptor Proteins, Vesicular Transport
Insect Science
Interferon Type I
Myeloid Differentiation Factor 88
DEAD Box Protein 58
Thogotovirus
Interferon type I
medicine.drug
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....2e64dd5de7816ffeaad01baa27366c15