Viral Evasion of Innate Immunity and Drug Development

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

Deadline for manuscript submissions: closed (15 April 2022) | Viewed by 11694

Special Issue Editors


E-Mail Website
Guest Editor
Chair, Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato SS554, Monserrato, 09042 Cagliari, Italy
Interests: virology; microbiology; antiviral drugs; drug development; endogenous retroviruses; innate immunity
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Equipe VIRIMI—Infections Virales, Métabolisme et Immunité Centre International de Recherche en Infectiologie (CIRI)—INSERM U1111—CNRS UMR5308 Université Lyon 1, 69365 Lyon, France
Interests: chemobiology; interferon; innate immunity; immunostimulatory molecules; immunometabolism; host-directed antivirals

Special Issue Information

Dear Colleagues,

Antiviral innate immunity is an ancestral defense system against viruses. It is essentially based on pattern recognition receptors (PRR) which recognize pathogen associated molecular patterns (PAMPs). In vertebrates, viral PAMPs activate signaling cascades leading to the production of cytokines, especially interferons (IFNs), and trigger critical antiviral mechanisms including: nuclease activation; translation inhibition; metabolic reprogramming; autophagy; cell death; and inflammation. On the one hand, pathogenic viruses have developed a variety of systems to evade innate immunity, while on the other hand, overactivation of the innate immune system can be deleterious to the individual, with the overproduction of cytokines and IFNs leading to pathological events. The Special Issue is devoted to (i) characterizing the mechanisms by which viral proteins evade the innate immune system; (ii) the development of drugs that are active on both viral and cellular proteins to counteract the immune evasion displayed by viruses; (iii) the development of drugs that shut off the innate immune system when overactivated in specific pathological conditions.

Prof. Dr. Enzo Tramontano
Prof. Dr. Pierre-Olivier Vidalain
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 submissions that pass pre-check are 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 2600 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

  • innate immunity
  • interferon (IFN)
  • viral evasion
  • drug development
  • viral inhibition
  • IFN production/signaling activation
  • IFN production/signaling inhibition
  • antiviral immunotherapy
  • host-directed antivirals

Published Papers (3 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

16 pages, 3169 KiB  
Article
INMI1 Zika Virus NS4B Antagonizes the Interferon Signaling by Suppressing STAT1 Phosphorylation
by Elisa Fanunza, Nicole Grandi, Marina Quartu, Fabrizio Carletti, Laura Ermellino, Jessica Milia, Angela Corona, Maria Rosaria Capobianchi, Giuseppe Ippolito and Enzo Tramontano
Viruses 2021, 13(12), 2448; https://doi.org/10.3390/v13122448 - 06 Dec 2021
Cited by 18 | Viewed by 2991
Abstract
The evasion of the Interferon response has important implications in Zika virus (ZIKV) disease. Mutations in ZIKV viral protein NS4B, associated with modulation of the interferon (IFN) system, have been linked to increased pathogenicity in animal models. In this study, we unravel ZIKV [...] Read more.
The evasion of the Interferon response has important implications in Zika virus (ZIKV) disease. Mutations in ZIKV viral protein NS4B, associated with modulation of the interferon (IFN) system, have been linked to increased pathogenicity in animal models. In this study, we unravel ZIKV NS4B as antagonist of the IFN signaling cascade. Firstly, we reported the genomic characterization of NS4B isolated from a strain of the 2016 outbreak, ZIKV Brazil/2016/INMI1, and we predicted its membrane topology. Secondly, we analyzed its phylogenetic correlation with other flaviviruses, finding a high similarity with dengue virus 2 (DEN2) strains; in particular, the highest conservation was found when NS4B was aligned with the IFN inhibitory domain of DEN2 NS4B. Hence, we asked whether ZIKV NS4B was also able to inhibit the IFN signaling cascade, as reported for DEN2 NS4B. Our results showed that ZIKV NS4B was able to strongly inhibit the IFN stimulated response element and the IFN-γ-activated site transcription, blocking IFN-I/-II responses. mRNA expression levels of the IFN stimulated genes ISG15 and OAS1 were also strongly reduced in presence of NS4B. We found that the viral protein was acting by suppressing the STAT1 phosphorylation and consequently blocking the nuclear transport of both STAT1 and STAT2. Full article
(This article belongs to the Special Issue Viral Evasion of Innate Immunity and Drug Development)
Show Figures

Figure 1

Review

Jump to: Research

21 pages, 1786 KiB  
Review
Characterization of SARS-CoV-2 Evasion: Interferon Pathway and Therapeutic Options
by Mariem Znaidia, Caroline Demeret, Sylvie van der Werf and Anastassia V. Komarova
Viruses 2022, 14(6), 1247; https://doi.org/10.3390/v14061247 - 08 Jun 2022
Cited by 21 | Viewed by 3358
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. SARS-CoV-2 is characterized by an important capacity to circumvent the innate immune response. The early interferon (IFN) response is necessary to establish a robust antiviral state. However, this response is [...] Read more.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. SARS-CoV-2 is characterized by an important capacity to circumvent the innate immune response. The early interferon (IFN) response is necessary to establish a robust antiviral state. However, this response is weak and delayed in COVID-19 patients, along with massive pro-inflammatory cytokine production. This dysregulated innate immune response contributes to pathogenicity and in some individuals leads to a critical state. Characterizing the interplay between viral factors and host innate immunity is crucial to better understand how to manage the disease. Moreover, the constant emergence of new SARS-CoV-2 variants challenges the efficacy of existing vaccines. Thus, to control this virus and readjust the antiviral therapy currently used to treat COVID-19, studies should constantly be re-evaluated to further decipher the mechanisms leading to SARS-CoV-2 pathogenesis. Regarding the role of the IFN response in SARS-CoV-2 infection, in this review we summarize the mechanisms by which SARS-CoV-2 evades innate immune recognition. More specifically, we explain how this virus inhibits IFN signaling pathways (IFN-I/IFN-III) and controls interferon-stimulated gene (ISG) expression. We also discuss the development and use of IFNs and potential drugs controlling the innate immune response to SARS-CoV-2, helping to clear the infection. Full article
(This article belongs to the Special Issue Viral Evasion of Innate Immunity and Drug Development)
Show Figures

Figure 1

26 pages, 1756 KiB  
Review
How Influenza A Virus NS1 Deals with the Ubiquitin System to Evade Innate Immunity
by Laurie-Anne Lamotte and Lionel Tafforeau
Viruses 2021, 13(11), 2309; https://doi.org/10.3390/v13112309 - 19 Nov 2021
Cited by 10 | Viewed by 4333
Abstract
Ubiquitination is a post-translational modification regulating critical cellular processes such as protein degradation, trafficking and signaling pathways, including activation of the innate immune response. Therefore, viruses, and particularly influenza A virus (IAV), have evolved different mechanisms to counteract this system to perform proper [...] Read more.
Ubiquitination is a post-translational modification regulating critical cellular processes such as protein degradation, trafficking and signaling pathways, including activation of the innate immune response. Therefore, viruses, and particularly influenza A virus (IAV), have evolved different mechanisms to counteract this system to perform proper infection. Among IAV proteins, the non-structural protein NS1 is shown to be one of the main virulence factors involved in these viral hijackings. NS1 is notably able to inhibit the host’s antiviral response through the perturbation of ubiquitination in different ways, as discussed in this review. Full article
(This article belongs to the Special Issue Viral Evasion of Innate Immunity and Drug Development)
Show Figures

Figure 1

Back to TopTop