Tick-Borne Flaviviruses and the Type I Interferon Response

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Abstract

Flaviviruses are globally distributed pathogens causing millions of human infections every year. Flaviviruses are arthropod-borne viruses and are mainly transmitted by either ticks or mosquitoes. Mosquito-borne flaviviruses and their interactions with the innate immune response have been well-studied and reviewed extensively, thus this review will discuss tick-borne flaviviruses and their interactions with the host innate immune response.

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Most cited references 141

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Antiviral actions of interferons.

C Samuel (2001)

Tremendous progress has been made in understanding the molecular basis of the antiviral actions of interferons (IFNs), as well as strategies evolved by viruses to antagonize the actions of IFNs. Furthermore, advances made while elucidating the IFN system have contributed significantly to our understanding in multiple areas of virology and molecular cell biology, ranging from pathways of signal transduction to the biochemical mechanisms of transcriptional and translational control to the molecular basis of viral pathogenesis. IFNs are approved therapeutics and have moved from the basic research laboratory to the clinic. Among the IFN-induced proteins important in the antiviral actions of IFNs are the RNA-dependent protein kinase (PKR), the 2',5'-oligoadenylate synthetase (OAS) and RNase L, and the Mx protein GTPases. Double-stranded RNA plays a central role in modulating protein phosphorylation and RNA degradation catalyzed by the IFN-inducible PKR kinase and the 2'-5'-oligoadenylate-dependent RNase L, respectively, and also in RNA editing by the IFN-inducible RNA-specific adenosine deaminase (ADAR1). IFN also induces a form of inducible nitric oxide synthase (iNOS2) and the major histocompatibility complex class I and II proteins, all of which play important roles in immune response to infections. Several additional genes whose expression profiles are altered in response to IFN treatment and virus infection have been identified by microarray analyses. The availability of cDNA and genomic clones for many of the components of the IFN system, including IFN-alpha, IFN-beta, and IFN-gamma, their receptors, Jak and Stat and IRF signal transduction components, and proteins such as PKR, 2',5'-OAS, Mx, and ADAR, whose expression is regulated by IFNs, has permitted the generation of mutant proteins, cells that overexpress different forms of the proteins, and animals in which their expression has been disrupted by targeted gene disruption. The use of these IFN system reagents, both in cell culture and in whole animals, continues to provide important contributions to our understanding of the virus-host interaction and cellular antiviral response.

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Jennifer Lund, Lena Alexopoulou, Ayuko Sato … (2004)

Viral infection of mammalian host results in the activation of innate immune responses. Toll-like receptors (TLRs) have been shown to mediate the recognition of many types of pathogens, including viruses. The genomes of viruses possess unique characteristics that are not found in mammalian genomes, such as high CpG content and double-stranded RNA. These genomic nucleic acids serve as molecular signatures associated with viral infections. Here we show that TLR7 recognizes the single-stranded RNA viruses, vesicular stomatitis virus and influenza virus. The recognition of these viruses by plasmacytoid dendritic cells and B cells through TLR7 results in their activation of costimulatory molecules and production of cytokines. Moreover, this recognition required intact endocytic pathways. Mice deficient in either the TLR7 or the TLR adaptor protein MyD88 demonstrated reduced responses to in vivo infection with vesicular stomatitis virus. These results demonstrate microbial ligand recognition by TLR7 and provide insights into the pathways used by the innate immune cells in the recognition of viral pathogens.

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IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors.

Kenya Honda, Tadatsugu Taniguchi (2006)

The interferon-regulatory factor (IRF) family of transcription factors was initially found to be involved in the induction of genes that encode type I interferons. IRFs have now been shown to have functionally diverse roles in the regulation of the immune system. Recently, the crucial involvement of IRFs in innate and adaptive immune responses has been gaining much attention, particularly with the discovery of their role in immunoregulation by Toll-like receptors and other pattern-recognition receptors.

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Author and article information

Journal

Journal ID (nlm-ta): Viruses

Journal ID (iso-abbrev): Viruses

Journal ID (publisher-id): viruses

Title: Viruses

Publisher: MDPI

ISSN (Electronic): 1999-4915

Publication date (Electronic): 21 June 2018

Publication date Collection: July 2018

Volume: 10

Issue: 7

Electronic Location Identifier: 340

Affiliations

[1 ]Department of Clinical Microbiology, Virology, Umeå University, SE-90185 Umeå, Sweden; richard.lindqvist@ 123456umu.se (R.L.); upadhyay.arunkumar@ 123456umu.se (A.U.)

[2 ]Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, SE-90187 Umeå, Sweden

[3 ]Umeå Centre for Microbial Research (UCMR), Umeå University, SE-90187 Umeå, Sweden

Author notes

[* ]Correspondence: Anna.Overby@ 123456umu.se ; Tel.: +46-90-7850922

[†]

Current address: Institut für Zytobiologie, Philipps-Universität Marburg, D-35032 Marburg, Germany.

Author information

Richard Lindqvist https://orcid.org/0000-0002-6103-8286

Anna K. Överby https://orcid.org/0000-0001-6553-0940

Article

Publisher ID: viruses-10-00340

DOI: 10.3390/v10070340

PMC ID: 6071234

PubMed ID: 29933625

SO-VID: 4fc8188e-694d-4c91-8151-aa297e7256e4

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Tick-Borne Flaviviruses and the Type I Interferon Response

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Abstract

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MDPI: Coronavirus

Most cited references 141

Antiviral actions of interferons.

Recognition of single-stranded RNA viruses by Toll-like receptor 7.

IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors.

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