Viral Proteins for Synthetic Biology

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Microenvironment".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 15709

Special Issue Editor


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Guest Editor
Department of Molecular and Translational Medicine, University of Brescia, Viale Europa, 11–25123 Brescia, Italy
Interests: HIV; human respiratory viruses; vaccines; gene therapy; viral oncology; cell/host interaction; endothelial cell dysfunction; cancer microenvironment; clinical virology
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Special Issue Information

Dear Colleagues,

The aim of this Special Issue is to offer an opportunity to collect the newest contributions in the field of biologically active viral proteins.

Synthetic biology underlies the possibility to control cells by introducing new molecules and networks. The aim of this Special Issue is to facilitate the exchange of information and promote scientific and technical knowledge relating to viruses that normally live in and among us for genetic blueprints that enable them to make biologically active molecules. These proteins may act as powerful tools for controlling cell biology and serve as the basis for developing new therapeutic drugs against different human diseases, including cancer. Viral proteins with novel functions will greatly improve the mechanistic knowledge about their activity and help us to design small, simple, and non-immunogenic polypeptides that are still able to achieve the desired biological activity. These minimalist proteins or peptides will represent future drugs to be used in humans.

All researchers working in the field are cordially invited to contribute with original research papers or propose reviews to this Special Issue of Cells.

Dr. Arnaldo Caruso
Guest Editor

Manuscript Submission Information

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Keywords

  • viral proteins
  • recombinant/synthetic viral proteins
  • biologically active viral proteins/peptides
  • virus/host interaction
  • vaccines
  • drug development

Published Papers (3 papers)

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Research

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18 pages, 2952 KiB  
Article
Avian Reovirus P17 Suppresses Angiogenesis by Promoting DPP4 Secretion
by Ekta Manocha, Antonella Bugatti, Mirella Belleri, Alberto Zani, Stefania Marsico, Francesca Caccuri, Marco Presta and Arnaldo Caruso
Cells 2021, 10(2), 259; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10020259 - 28 Jan 2021
Cited by 7 | Viewed by 2520
Abstract
Avian reovirus p17 (ARV p17) is a non-structural protein known to activate autophagy, interfere with gene transcription and induce a significant tumor cell growth inhibition in vitro and in vivo. In this study, we show that ARV p17 is capable of exerting potent [...] Read more.
Avian reovirus p17 (ARV p17) is a non-structural protein known to activate autophagy, interfere with gene transcription and induce a significant tumor cell growth inhibition in vitro and in vivo. In this study, we show that ARV p17 is capable of exerting potent antiangiogenic properties. The viral protein significantly inhibited the physiological angiogenesis of human endothelial cells (ECs) by affecting migration, capillary-like structure and new vessel formation. ARV p17 was not only able to suppress the EC physiological angiogenesis but also rendered ECs insensitive to two different potent proangiogenic inducers, such as VEGF-A and FGF-2 in the three-dimensional (3D) Matrigel and spheroid assay. ARV p17 was found to exert its antiangiogenic activity by upregulating transcription and release of the well-known tumor suppressor molecule dipeptidyl peptidase 4 (DPP4). The ability of ARV p17 to impact on angiogenesis is completely new and highlights the “two compartments” activity of the viral protein that is expected to hamper the tumor parenchymal/stromal crosstalk. The complex antitumor activities of ARV p17 open the way to a new promising field of research aimed to develop new therapeutic approaches for treating tumor and cancer metastasis. Full article
(This article belongs to the Special Issue Viral Proteins for Synthetic Biology)
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15 pages, 3036 KiB  
Article
SARS-CoV-2 Spike 1 Protein Controls Natural Killer Cell Activation via the HLA-E/NKG2A Pathway
by Daria Bortolotti, Valentina Gentili, Sabrina Rizzo, Antonella Rotola and Roberta Rizzo
Cells 2020, 9(9), 1975; https://0-doi-org.brum.beds.ac.uk/10.3390/cells9091975 - 26 Aug 2020
Cited by 70 | Viewed by 8551
Abstract
Natural killer cells are important in the control of viral infections. However, the role of NK cells during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has previously not been identified. Peripheral blood NK cells from SARS-CoV and SARS-CoV-2 naïve subjects were evaluated [...] Read more.
Natural killer cells are important in the control of viral infections. However, the role of NK cells during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has previously not been identified. Peripheral blood NK cells from SARS-CoV and SARS-CoV-2 naïve subjects were evaluated for their activation, degranulation, and interferon-gamma expression in the presence of SARS-CoV and SARS-CoV-2 spike proteins. K562 and lung epithelial cells were transfected with spike proteins and co-cultured with NK cells. The analysis was performed by flow cytometry and immune fluorescence. SARS-CoV and SARS-CoV-2 spike proteins did not alter NK cell activation in a K562 in vitro model. On the contrary, SARS-CoV-2 spike 1 protein (SP1) intracellular expression by lung epithelial cells resulted in NK cell-reduced degranulation. Further experiments revealed a concomitant induction of HLA-E expression on the surface of lung epithelial cells and the recognition of an SP1-derived HLA-E-binding peptide. Simultaneously, there was increased modulation of the inhibitory receptor NKG2A/CD94 on NK cells when SP1 was expressed in lung epithelial cells. We ruled out the GATA3 transcription factor as being responsible for HLA-E increased levels and HLA-E/NKG2A interaction as implicated in NK cell exhaustion. We show for the first time that NK cells are affected by SP1 expression in lung epithelial cells via HLA-E/NKG2A interaction. The resulting NK cells’ exhaustion might contribute to immunopathogenesis in SARS-CoV-2 infection. Full article
(This article belongs to the Special Issue Viral Proteins for Synthetic Biology)
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Review

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18 pages, 2475 KiB  
Review
The U94 Gene of Human Herpesvirus 6: A Narrative Review of Its Role and Potential Functions
by Elisabetta Caselli, Maria D’Accolti, Francesca Caccuri, Irene Soffritti, Valentina Gentili, Daria Bortolotti, Antonella Rotola, Enzo Cassai, Simona Fiorentini, Alberto Zani, Arnaldo Caruso, Roberta Rizzo and Dario Di Luca
Cells 2020, 9(12), 2608; https://0-doi-org.brum.beds.ac.uk/10.3390/cells9122608 - 4 Dec 2020
Cited by 13 | Viewed by 3937
Abstract
Human herpesvirus 6 (HHV-6) is a β-herpesvirus that is highly prevalent in the human population. HHV-6 comprises two recognized species (HHV-6A and HHV-6B). Despite different cell tropism and disease association, HHV-6A/B show high genome homology and harbor the conserved U94 gene, which is [...] Read more.
Human herpesvirus 6 (HHV-6) is a β-herpesvirus that is highly prevalent in the human population. HHV-6 comprises two recognized species (HHV-6A and HHV-6B). Despite different cell tropism and disease association, HHV-6A/B show high genome homology and harbor the conserved U94 gene, which is limited to HHV-6 and absent in all the other human herpesviruses. U94 has key functions in the virus life cycle and associated diseases, having demonstrated or putative roles in virus replication, integration, and reactivation. During natural infection, U94 elicits an immune response, and the prevalence and extent of the anti-U94 response are associated with specific diseases. Notably, U94 can entirely reproduce some virus effects at the cell level, including inhibition of cell migration, induction of cytokines and HLA-G expression, and angiogenesis inhibition, supporting a direct U94 role in the development of HHV-6-associated diseases. Moreover, specific U94 properties, such as the ability to modulate angiogenesis pathways, have been exploited to counteract cancer development. Here, we review the information available on this key HHV-6 gene, highlighting its potential uses. Full article
(This article belongs to the Special Issue Viral Proteins for Synthetic Biology)
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