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Viruses
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15th International Adenovirus Meeting
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15th International Adenovirus Meeting

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "General Virology".

Deadline for manuscript submissions: closed (31 July 2024) | Viewed by 13623

Special Issue Editors

Dr. Dragomira Majhen

E-Mail Website
Guest Editor
Ruđer Bošković Institute, Division of molecular biology, 10 000 Zagreb, Croatia
Interests: adenovirus vectors; targeting; endocytosis; host response
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Alan Parker

E-Mail Website
Guest Editor
Division of Cancer and Genetics, School of Medicine, Cardiff CF14 4XN, UK
Interests: .oncolytic adenoviruses; cancer gene therapy; adenovirus targeting
Prof. Dr. David T. Curiel

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Guest Editor
Biologic Therapeutics Center Washington University School of Medicine Department of Radiation Oncology, St. Louis, MO, USA
Interests: gene therapy; adenovirus; virotherapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Adenoviruses can cause mild health problems, such as acute respiratory, gastrointestinal, and ocular infections, but have no oncogenic potential in humans. Nevertheless, they can cause severe, even life-threatening, pathologies in immunosuppressed individuals. No efficient treatment for adenovirus infections has been approved so far. Besides humans, adenoviruses can also infect domestic animals, resulting in economic losses. However, adenoviruses represent exceptional candidates for wide-ranging therapeutic applications, from vectors for gene therapy to oncolytics for cancer treatments. The first ever commercial gene therapy medicine was based on a recombinant adenovirus vector, while most recently, adenoviral vectors have proven critical as vaccine platforms in effectively controlling the global coronavirus pandemic. Besides being used in therapeutic approaches, adenoviruses have also been popular model systems for studying viral entry, transcription and replication of the DNA genome, mRNA splicing, the expression of proteins, virus assembly, cell cycle control, cellular growth, the transformation of cells in vitro, and tumorigenesis.

The exchange of ideas and information among scientists working in all aspects of adenovirus biology and applications is fundamental to advance our ability to fight against adenovirus-induced disease, and to repurpose the virus as an efficient tool in biomedicine. Therefore, for this Special Issue, we welcome the most recent advances in adenovirus research in any paper format, including short and regular original articles and reviews. For participants of the 15th International Adenovirus Meeting in Croatia (https://event.fourwaves.com/iam2023/pages), a 20% discount on Article Processing Charges will be applied.

Dr. Dragomira Majhen
Prof. Dr. Alan Parker
Prof. Dr. David T. Curiel
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

  • human and non-human adenovirus
  • virus–host response
  • receptors
  • immunology and pathogenesis
  • epidemiology
  • oncolytic vectors
  • vaccines
  • structure and assembly
  • entry and cell trafficking
  • life cycle
  • antiviral targets

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Published Papers (6 papers)

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Research

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13 pages, 1586 KiB  
Article
CD46 Is a Protein Receptor for Human Adenovirus Type 64
by Eugene Y. Wu, Alexander M. Robertson, Hanglin (Henry) Zhu, Corina Stasiak, Laura A. Murray-Nerger, Emily Romanoff, Jesse Woon, Beth A. Bromme and Jason G. Smith
Viruses 2024, 16(12), 1827; https://doi.org/10.3390/v16121827 - 25 Nov 2024
Viewed by 1475
Abstract
Certain species D human adenoviruses (HAdV-D19, -D37, and -D64) are causative agents of epidemic keratoconjunctivitis. HAdV-D37 has previously been shown to bind CD46 (membrane cofactor protein) and sialic acid as adhesion receptors. HAdV-D64 is genetically highly similar to HAdV-D37, with an identical fiber [...] Read more.
Certain species D human adenoviruses (HAdV-D19, -D37, and -D64) are causative agents of epidemic keratoconjunctivitis. HAdV-D37 has previously been shown to bind CD46 (membrane cofactor protein) and sialic acid as adhesion receptors. HAdV-D64 is genetically highly similar to HAdV-D37, with an identical fiber protein sequence, but differs substantially in its penton base and hexon proteins, two other major capsid components, due to genetic recombination. Here, we demonstrate that, like HAdV-D37, HAdV-D64 virions bind directly to CD46 and that CD46 and sialic acid also function as receptors for HAdV-D64 on multiple cell types. Expression of CD46 on CD46-negative cells conferred susceptibility to HAdV-D64 entry. Specifically blocking HAdV-D64 binding to CD46 on the host cell surface strongly inhibits viral entry and gene delivery into multiple cell lines that represent target tissues. We show that CD46 is expressed on human conjunctival epithelial cells and directly binds to the HAdV-D64 virion. Our results suggest that HAdV-D64 may be used to deliver genes to target conjunctival cells and that interrupting HAdV-D64 entry through its interaction with CD46 may prevent or lessen adenovirus-associated ocular disease. Full article
(This article belongs to the Special Issue 15th International Adenovirus Meeting)
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16 pages, 2504 KiB  
Article
Expanding the Scope of Adenoviral Vectors by Utilizing Novel Tools for Recombination and Vector Rescue
by Julian Fischer, Ariana Fedotova, Clara Bühler, Laura Darriba, Sabrina Schreiner and Zsolt Ruzsics
Viruses 2024, 16(5), 658; https://doi.org/10.3390/v16050658 - 23 Apr 2024
Cited by 1 | Viewed by 1385
Abstract
Recombinant adenoviruses are widely used in clinical and laboratory applications. Despite the wide variety of available sero- and genotypes, only a fraction is utilized in vivo. As adenoviruses are a large group of viruses, displaying many different tropisms, immune epitopes, and replication characteristics, [...] Read more.
Recombinant adenoviruses are widely used in clinical and laboratory applications. Despite the wide variety of available sero- and genotypes, only a fraction is utilized in vivo. As adenoviruses are a large group of viruses, displaying many different tropisms, immune epitopes, and replication characteristics, the merits of translating these natural benefits into vector applications are apparent. This translation, however, proves difficult, since while research has investigated the application of these viruses, there are no universally applicable rules in vector design for non-classical adenovirus types. In this paper, we describe a generalized workflow that allows vectorization, rescue, and cloning of all adenoviral species to enable the rapid development of new vector variants. We show this using human and simian adenoviruses, further modifying a selection of them to investigate their gene transfer potential and build potential vector candidates for future applications. Full article
(This article belongs to the Special Issue 15th International Adenovirus Meeting)
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25 pages, 7809 KiB  
Article
Oncolytic Adenovirus for the Targeting of Paclitaxel-Resistant Breast Cancer Stem Cells
by Sacha Robert, Natasha Ivelisse Roman Ortiz, Christopher J. LaRocca, Julie Hanson Ostrander and Julia Davydova
Viruses 2024, 16(4), 567; https://doi.org/10.3390/v16040567 - 5 Apr 2024
Cited by 2 | Viewed by 2254
Abstract
Adjuvant systemic therapies effectively reduce the risk of breast cancer recurrence and metastasis, but therapy resistance can develop in some patients due to breast cancer stem cells (BCSCs). Oncolytic adenovirus (OAd) represents a promising therapeutic approach as it can specifically target cancer cells. [...] Read more.
Adjuvant systemic therapies effectively reduce the risk of breast cancer recurrence and metastasis, but therapy resistance can develop in some patients due to breast cancer stem cells (BCSCs). Oncolytic adenovirus (OAd) represents a promising therapeutic approach as it can specifically target cancer cells. However, its potential to target BCSCs remains unclear. Here, we evaluated a Cox-2 promoter-controlled, Ad5/3 fiber-modified OAd designed to encode the human sodium iodide symporter (hNIS) in breast cancer models. To confirm the potential of OAds to target BCSCs, we employed BCSC-enriched estrogen receptor-positive (ER+) paclitaxel-resistant (TaxR) cells and tumorsphere assays. OAd-hNIS demonstrated significantly enhanced binding and superior oncolysis in breast cancer cells, including ER+ cells, while exhibiting no activity in normal mammary epithelial cells. We observed improved NIS expression as the result of adenovirus death protein deletion. OAd-hNIS demonstrated efficacy in targeting TaxR BCSCs, exhibiting superior killing and hNIS expression compared to the parental cells. Our vector was capable of inhibiting tumorsphere formation upon early infection and reversing paclitaxel resistance in TaxR cells. Importantly, OAd-hNIS also destroyed already formed tumorspheres seven days after their initiation. Overall, our findings highlight the promise of OAd-hNIS as a potential tool for studying and targeting ER+ breast cancer recurrence and metastasis. Full article
(This article belongs to the Special Issue 15th International Adenovirus Meeting)
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20 pages, 3382 KiB  
Article
Identification of Adenovirus E1B-55K Interaction Partners through a Common Binding Motif
by Nafiseh Chalabi Hagkarim, Wing-Hang Ip, Luca D. Bertzbach, Tareq Abualfaraj, Thomas Dobner, David P. Molloy, Grant S. Stewart and Roger J. Grand
Viruses 2023, 15(12), 2356; https://doi.org/10.3390/v15122356 - 30 Nov 2023
Cited by 1 | Viewed by 2272
Abstract
The adenovirus C5 E1B-55K protein is crucial for viral replication and is expressed early during infection. It can interact with E4orf6 to form a complex that functions as a ubiquitin E3 ligase. This complex targets specific cellular proteins and marks them for ubiquitination [...] Read more.
The adenovirus C5 E1B-55K protein is crucial for viral replication and is expressed early during infection. It can interact with E4orf6 to form a complex that functions as a ubiquitin E3 ligase. This complex targets specific cellular proteins and marks them for ubiquitination and, predominantly, subsequent proteasomal degradation. E1B-55K interacts with various proteins, with p53 being the most extensively studied, although identifying binding sites has been challenging. To explain the diverse range of proteins associated with E1B-55K, we hypothesized that other binding partners might recognize the simple p53 binding motif (xWxxxPx). In silico analyses showed that many known E1B-55K binding proteins possess this amino acid sequence; therefore, we investigated whether other xWxxxPx-containing proteins also bind to E1B-55K. Our findings revealed that many cellular proteins, including ATR, CHK1, USP9, and USP34, co-immunoprecipitate with E1B-55K. During adenovirus infection, several well-characterized E1B-55K binding proteins and newly identified interactors, including CSB, CHK1, and USP9, are degraded in a cullin-dependent manner. Notably, certain binding proteins, such as ATR and USP34, remain undegraded during infection. Structural predictions indicate no conservation of structure around the proposed binding motif, suggesting that the interaction relies on the correct arrangement of tryptophan and proline residues. Full article
(This article belongs to the Special Issue 15th International Adenovirus Meeting)
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16 pages, 2680 KiB  
Article
Engineering a Novel Modular Adenoviral mRNA Delivery Platform Based on Tag/Catcher Bioconjugation
by Kexin Geng, Paul J. Rice-Boucher, Elena A. Kashentseva, Igor P. Dmitriev, Zhi Hong Lu, S. Peter Goedegebuure, William E. Gillanders and David T. Curiel
Viruses 2023, 15(11), 2277; https://doi.org/10.3390/v15112277 - 20 Nov 2023
Cited by 1 | Viewed by 2094
Abstract
mRNA vaccines have attracted widespread research attention with clear advantages in terms of molecular flexibility, rapid development, and potential for personalization. However, current mRNA vaccine platforms have not been optimized for induction of CD4/CD8 T cell responses. In addition, the mucosal administration of [...] Read more.
mRNA vaccines have attracted widespread research attention with clear advantages in terms of molecular flexibility, rapid development, and potential for personalization. However, current mRNA vaccine platforms have not been optimized for induction of CD4/CD8 T cell responses. In addition, the mucosal administration of mRNA based on lipid nanoparticle technology faces challenges in clinical translation. In contrast, adenovirus-based vaccines induce strong T cell responses and have been approved for intranasal delivery. To leverage the inherent strengths of both the mRNA and adenovirus platforms, we developed a novel modular adenoviral mRNA delivery platform based on Tag/Catcher bioconjugation. Specifically, we engineered adenoviral vectors integrating Tag/Catcher proteins at specific locales on the Ad capsid proteins, allowing us to anchor mRNA to the surface of engineered Ad viruses. In proof-of-concept studies, the Ad-mRNA platform successfully mediated mRNA delivery and could be optimized via the highly flexible modular design of both the Ad-mRNA and protein bioconjugation systems. Full article
(This article belongs to the Special Issue 15th International Adenovirus Meeting)
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Review

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44 pages, 4889 KiB  
Review
The Immune System—A Double-Edged Sword for Adenovirus-Based Therapies
by Rebecca Wallace, Carly M. Bliss and Alan L. Parker
Viruses 2024, 16(6), 973; https://doi.org/10.3390/v16060973 - 17 Jun 2024
Cited by 3 | Viewed by 2893
Abstract
Pathogenic adenovirus (Ad) infections are widespread but typically mild and transient, except in the immunocompromised. As vectors for gene therapy, vaccine, and oncology applications, Ad-based platforms offer advantages, including ease of genetic manipulation, scale of production, and well-established safety profiles, making them attractive [...] Read more.
Pathogenic adenovirus (Ad) infections are widespread but typically mild and transient, except in the immunocompromised. As vectors for gene therapy, vaccine, and oncology applications, Ad-based platforms offer advantages, including ease of genetic manipulation, scale of production, and well-established safety profiles, making them attractive tools for therapeutic development. However, the immune system often poses a significant challenge that must be overcome for adenovirus-based therapies to be truly efficacious. Both pre-existing anti-Ad immunity in the population as well as the rapid development of an immune response against engineered adenoviral vectors can have detrimental effects on the downstream impact of an adenovirus-based therapeutic. This review focuses on the different challenges posed, including pre-existing natural immunity and anti-vector immunity induced by a therapeutic, in the context of innate and adaptive immune responses. We summarise different approaches developed with the aim of tackling these problems, as well as their outcomes and potential future applications. Full article
(This article belongs to the Special Issue 15th International Adenovirus Meeting)
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