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Special Issue "IFN-Independent ISG Expression and Its Role in Antiviral Cell-Intrinsic Innate Immunity"

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Antivirals & Vaccines".

Deadline for manuscript submissions: 15 April 2019

Special Issue Editors

Guest Editor
Dr. Emmanuel Thomas

Department of Microbiology and Immunology, University of Miami Miller School of Medicine, USA
Website | E-Mail
Interests: virology; antivirals; hepatitis viruses; cell-intrinsic innate immunity; virus–host interaction; viral oncology
Guest Editor
Dr. Takeshi Saito

Department of Medicine, Molecular Microbiology & Immunology, and Pathology, University of Southern California, Keck School of Medicine, USA
Website | E-Mail
Interests: virology; hepatitis viruses; cell-intrinsic innate immunity; virus–host interaction; host defense; interferon

Special Issue Information

Dear Colleagues,

Over the last few decades, accumulating evidence has demonstrated that many Interferon (IFN) stimulate genes (ISGs) can be directly upregulated by viruses independent of IFN signaling, and they have been called virus stimulated genes (VSGs). Indeed, whereas typical ISGs are driven by JAK-STAT signaling, VSG are upregulated through the IRF3 and NF-κB pathways. IFNs themselves are VSGs.  Interestingly, VSGs have natural anticancer activities, and they may cause diseases in humans when induced chronically. To understand their role in host defense and pathogenesis, excellent model systems have been developed. However, there are still important gaps in our understanding of VSGs and host defense. Recently, RNA sequencing techniques have allowed the discovery of novel VSGs that also include non-coding RNAs. This Special Issue of Viruses will explore the impact of VSGs on the outcome of virus infection and of the role of these genes within the infected cells and organism. We will also focus on the most recent discoveries in VSG research, including the molecular biology of related virus–host interactions. Topics may include studies on various steps of gene induction, virus adaptation to VSGs, innate immune responses to virus infection, and mechanisms of virus immune evasion of related host defense pathways.  The clinical presentation of VSG-driven pathology and strategies to use VSGs to cure chronic viral infections will also be a focus.  In this Special Issue, we hope to assemble a collection of research papers and reviews that together will offer a comprehensive view on VSGs. Topics can include any aspects of VSGs and related biology; however, priority will be given to publications that utilize primary or iPSC derived-cells and/or patient samples/mouse models to validate data from in vitro studies. All submitted reviews should describe the precise regulation of the ISG/VSG that the authors have decided to write about.

 

Dr. Emmanuel Thomas
Dr. Takeshi Saito
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • ISGs host defense
  • VSGs and viral adaptation/evolution
  • VSGs and therapeutics
  • ISG antivirals
  • molecular biology of host defense
  • virus-host cell interactions
  • antivirals targeting VSGs
  • ISG pathogenesis and animal models

Published Papers (3 papers)

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Research

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Open AccessArticle Interferon-Independent Upregulation of Interferon-Stimulated Genes during Human Cytomegalovirus Infection is Dependent on IRF3 Expression
Viruses 2019, 11(3), 246; https://doi.org/10.3390/v11030246
Received: 31 January 2019 / Revised: 25 February 2019 / Accepted: 7 March 2019 / Published: 12 March 2019
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Abstract
The antiviral activity of type I interferons (IFNs) is primarily mediated by interferon-stimulated genes (ISGs). Induction of ISG transcription is achieved when type I IFNs bind to their cognate receptor and activate the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signaling pathways. [...] Read more.
The antiviral activity of type I interferons (IFNs) is primarily mediated by interferon-stimulated genes (ISGs). Induction of ISG transcription is achieved when type I IFNs bind to their cognate receptor and activate the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signaling pathways. Recently it has become clear that a number of viruses are capable of directly upregulating a subset of ISGs in the absence of type I IFN production. Using cells engineered to block either the response to, or production of type I IFN, the regulation of IFN-independent ISGs was examined in the context of human cytomegalovirus (HCMV) infection. Several ISGs, including IFIT1, IFIT2, IFIT3, Mx1, Mx2, CXCL10 and ISG15 were found to be upregulated transcriptionally following HCMV infection independently of type I IFN-initiated JAK-STAT signaling, but dependent on intact IRF3 signaling. ISG15 protein regulation mirrored that of its transcript with IFNβ neutralization failing to completely inhibit ISG15 expression post HCMV infection. In addition, no detectable ISG15 protein expression was observed following HCMV infection in IRF3 knockdown CRISPR/Cas-9 clones indicating that IFN-independent control of ISG expression during HCMV infection of human fibroblasts is absolutely dependent on IRF3 expression. Full article
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Open AccessArticle THO Complex Subunit 7 Homolog Negatively Regulates Cellular Antiviral Response against RNA Viruses by Targeting TBK1
Viruses 2019, 11(2), 158; https://doi.org/10.3390/v11020158
Received: 7 December 2018 / Revised: 5 February 2019 / Accepted: 12 February 2019 / Published: 15 February 2019
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Abstract
RNA virus invasion induces a cytosolic RIG-I-like receptor (RLR) signaling pathway by promoting assembly of the Mitochondrial antiviral-signaling protein (MAVS) signalosome and triggers the rapid production of type I interferons (IFNs) and proinflammatory cytokines. During this process, the pivotal kinase TANK binding kinase [...] Read more.
RNA virus invasion induces a cytosolic RIG-I-like receptor (RLR) signaling pathway by promoting assembly of the Mitochondrial antiviral-signaling protein (MAVS) signalosome and triggers the rapid production of type I interferons (IFNs) and proinflammatory cytokines. During this process, the pivotal kinase TANK binding kinase 1 (TBK1) is recruited to the MAVS signalosome to transduce a robust innate antiviral immune response by phosphorylating transcription factors interferon regulatory factor 3 (IRF3) and nuclear factor (NF)-κB and promoting their nuclear translocation. However, the molecular mechanisms underlying the negative regulation of TBK1 are largely unknown. In the present study, we found that THO complex subunit 7 homolog (THOC7) negatively regulated the cellular antiviral response by promoting the proteasomal degradation of TBK1. THOC7 overexpression potently inhibited Sendai virus- or polyI:C-induced IRF3 dimerization and phosphorylation and IFN-β production. In contrast, THOC7 knockdown had the opposite effects. Moreover, we simulated a node-activated pathway to show that THOC7 regulated the RIG-I-like receptors (RLR)-/MAVS-dependent signaling cascade at the TBK1 level. Furthermore, THOC7 was involved in the MAVS signalosome and promoted TBK1 degradation by increasing its K48 ubiquitin-associated polyubiquitination. Together, these findings suggest that THOC7 negatively regulates type I IFN production by promoting TBK1 proteasomal degradation, thus improving our understanding of innate antiviral immune responses. Full article
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Review

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Open AccessReview Rhabdoviruses, Antiviral Defense, and SUMO Pathway
Viruses 2018, 10(12), 686; https://doi.org/10.3390/v10120686
Received: 10 October 2018 / Revised: 13 November 2018 / Accepted: 28 November 2018 / Published: 3 December 2018
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Abstract
Small Ubiquitin-like MOdifier (SUMO) conjugation to proteins has essential roles in several processes including localization, stability, and function of several players implicated in intrinsic and innate immunity. In human, five paralogs of SUMO are known of which three are ubiquitously expressed (SUMO1, 2, [...] Read more.
Small Ubiquitin-like MOdifier (SUMO) conjugation to proteins has essential roles in several processes including localization, stability, and function of several players implicated in intrinsic and innate immunity. In human, five paralogs of SUMO are known of which three are ubiquitously expressed (SUMO1, 2, and 3). Infection by rhabdoviruses triggers cellular responses through the activation of pattern recognition receptors, which leads to the production and secretion of interferon. This review will focus on the effects of the stable expression of the different SUMO paralogs or Ubc9 depletion on rhabdoviruses-induced interferon production and interferon signaling pathways as well as on the expression and functions of restriction factors conferring the resistance to rhabdoviruses. Full article
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Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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