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Viruses
Special Issues
Adenovirus Cell and Immune Interactions 2.0
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Adenovirus Cell and Immune Interactions 2.0

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 June 2022) | Viewed by 9201

Special Issue Editor

Prof. Dr. Glen R. Nemerow

E-Mail Website
Guest Editor
Scripps Research Institute, Department of Microbiology and Immunology, San Diego, USA
Interests: virus-host receptor interactions; adenovirus structural biology; adenovirus-innate immune interactions
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Ever since their discovery in the early 1950s, human adenoviruses (HAdVs), the cause of respiratory diseases of young children, have been the subject of intense basic research as well as efforts to engineer HAdV vectors to ameliorate human diseases. Although much information has been gleaned over the past 67 years from laboratory and clinical investigations, we still have an incomplete picture of the critical associations of HAdV with host cells and specific components of the immune system. An ability to uncover additional information will likely influence the future success (or failure) for exploiting HAdV vectors for gene and vaccine therapies.

Each contribution in this series will highlight the efforts and progress made to acquire basic knowledge of adenovirus host interactions and will indicate particular areas that remain to be uncovered. Topics in this new series include key steps in HAdV–host cell entry and immune interactions as well as structure-based investigations of virus and virus capsid protein associations with cell receptors and innate immune molecules. Involvement of HAd in human diseases such as ocular pathogenesis will be also described. Genetic and chemical approaches to alter the Ad capsid to avoid immune interactions as well as structural and functional analyses of “immunoprivileged” HAdV26 and HAd49 vaccine candidate vectors will also be discussed.

Prof. Dr. Glen R. Nemerow
Guest Editor

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

  • adenovirus
  • gene therapy
  • ad vaccine
  • innate immune system
  • respiratory disease

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Published Papers (2 papers)

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Research

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22 pages, 3347 KiB  
Article
Sequence-Specific Features of Short Double-Strand, Blunt-End RNAs Have RIG-I- and Type 1 Interferon-Dependent or -Independent Anti-Viral Effects
by Abhilash Kannan, Maarit Suomalainen, Romain Volle, Michael Bauer, Marco Amsler, Hung V. Trinh, Stefano Vavassori, Jana Pachlopnik Schmid, Guilherme Vilhena, Alberto Marín-González, Ruben Perez, Andrea Franceschini, Christian von Mering, Silvio Hemmi and Urs F. Greber
Viruses 2022, 14(7), 1407; https://doi.org/10.3390/v14071407 - 28 Jun 2022
Cited by 1 | Viewed by 5191
Abstract
Pathogen-associated molecular patterns, including cytoplasmic DNA and double-strand (ds)RNA trigger the induction of interferon (IFN) and antiviral states protecting cells and organisms from pathogens. Here we discovered that the transfection of human airway cell lines or non-transformed fibroblasts with 24mer dsRNA mimicking the [...] Read more.
Pathogen-associated molecular patterns, including cytoplasmic DNA and double-strand (ds)RNA trigger the induction of interferon (IFN) and antiviral states protecting cells and organisms from pathogens. Here we discovered that the transfection of human airway cell lines or non-transformed fibroblasts with 24mer dsRNA mimicking the cellular micro-RNA (miR)29b-1* gives strong anti-viral effects against human adenovirus type 5 (AdV-C5), influenza A virus X31 (H3N2), and SARS-CoV-2. These anti-viral effects required blunt-end complementary RNA strands and were not elicited by corresponding single-strand RNAs. dsRNA miR-29b-1* but not randomized miR-29b-1* mimics induced IFN-stimulated gene expression, and downregulated cell adhesion and cell cycle genes, as indicated by transcriptomics and IFN-I responsive Mx1-promoter activity assays. The inhibition of AdV-C5 infection with miR-29b-1* mimic depended on the IFN-alpha receptor 2 (IFNAR2) and the RNA-helicase retinoic acid-inducible gene I (RIG-I) but not cytoplasmic RNA sensors MDA5 and ZNFX1 or MyD88/TRIF adaptors. The antiviral effects of miR29b-1* were independent of a central AUAU-motif inducing dsRNA bending, as mimics with disrupted AUAU-motif were anti-viral in normal but not RIG-I knock-out (KO) or IFNAR2-KO cells. The screening of a library of scrambled short dsRNA sequences identified also anti-viral mimics functioning independently of RIG-I and IFNAR2, thus exemplifying the diverse anti-viral mechanisms of short blunt-end dsRNAs. Full article
(This article belongs to the Special Issue Adenovirus Cell and Immune Interactions 2.0)
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Review

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20 pages, 1630 KiB  
Review
Cytokine Responses to Adenovirus and Adenovirus Vectors
by Svetlana Atasheva and Dmitry M. Shayakhmetov
Viruses 2022, 14(5), 888; https://doi.org/10.3390/v14050888 - 24 Apr 2022
Cited by 22 | Viewed by 3604
Abstract
The expression of cytokines and chemokines in response to adenovirus infection is tightly regulated by the innate immune system. Cytokine-mediated toxicity and cytokine storm are known clinical phenomena observed following naturally disseminated adenovirus infection in immunocompromised hosts as well as when extremely high [...] Read more.
The expression of cytokines and chemokines in response to adenovirus infection is tightly regulated by the innate immune system. Cytokine-mediated toxicity and cytokine storm are known clinical phenomena observed following naturally disseminated adenovirus infection in immunocompromised hosts as well as when extremely high doses of adenovirus vectors are injected intravenously. This dose-dependent, cytokine-mediated toxicity compromises the safety of adenovirus-based vectors and represents a critical problem, limiting their utility for gene therapy applications and the therapy of disseminated cancer, where intravenous injection of adenovirus vectors may provide therapeutic benefits. The mechanisms triggering severe cytokine response are not sufficiently understood, prompting efforts to further investigate this phenomenon, especially in clinically relevant settings. In this review, we summarize the current knowledge on cytokine and chemokine activation in response to adenovirus- and adenovirus-based vectors and discuss the underlying mechanisms that may trigger acute cytokine storm syndrome. First, we review profiles of cytokines and chemokines that are activated in response to adenovirus infection initiated via different routes. Second, we discuss the molecular mechanisms that lead to cytokine and chemokine transcriptional activation. We further highlight how immune cell types in different organs contribute to synthesis and systemic release of cytokines and chemokines in response to adenovirus sensing. Finally, we review host factors that can limit cytokine and chemokine expression and discuss currently available and potential future interventional approaches that allow for the mitigation of the severity of the cytokine storm syndrome. Effective cytokine-targeted interventional approaches may improve the safety of systemic adenovirus delivery and thus broaden the potential clinical utility of adenovirus-based therapeutic vectors. Full article
(This article belongs to the Special Issue Adenovirus Cell and Immune Interactions 2.0)
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