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Viruses
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Poxvirus
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Poxvirus

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

Deadline for manuscript submissions: closed (15 May 2022) | Viewed by 16368

Special Issue Editors

Prof. Dr. Flavio Guimaraes da Fonseca

E-Mail Website
Guest Editor
Vaccine Development Center, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Brazil
Interests: viral vaccines; viral diagnostics; nanomaterials applied to viral biotechnologies
Special Issues, Collections and Topics in MDPI journals
Dr. Erna G. Kroon

E-Mail Website
Guest Editor
Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil
Interests: Orthopoxvirus; vaccinia virus; giant viruses; yellow fever virus; dengue virus, Zika virus

Special Issue Information

Dear Colleagues,

Poxviruses have been at the very center of virology science development since its first years. Poxviruses were also present at the birth of vaccinology, and smallpox is the only human virus, to date, to be eradicated through a vaccination campaign. Viruses belonging to the Poxvirus family were among the first to be chemically characterized, grown in cell culture, purified, and accurately titrated. Moreover, poxviruses were also among the first to be used as biotechnological tools for the expression of heterologous proteins in mammalian cells. Today, poxviruses are still viewed as iconic viruses and are studied in a multitude of different contexts. This Special Issue aims to publish all types of manuscripts (i.e., reviews, research articles, and short communications) covering a wide range of topics related to poxviruses, including but not limited to the biology of poxviruses, pathogenesis of poxviruses and virus–host interactions, immune responses to poxviruses, ecology of poxviruses, identification of new species and/or new poxvirus variants, use of poxviruses as biotechnological tools, poxvirus-based vaccines, and oncolytic poxviruses

Dr. Flavio Guimaraes da Fonseca
Dr. Erna G. Kroon
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

  • poxvirus
  • vaccinia virus
  • zoonosis
  • oncolytic viruses
  • emergent viruses
  • smallpox
  • vaccine vectors
  • MVA
  • nucleocytoplasmic large DNA viruses (NCLDV)
  • oncolytic virus therapy

Published Papers (7 papers)

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Research

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18 pages, 2954 KiB  
Article
Crocodilepox Virus Protein 157 Is an Independently Evolved Inhibitor of Protein Kinase R
by M. Julhasur Rahman, Loubna Tazi, Sherry L. Haller and Stefan Rothenburg
Viruses 2022, 14(7), 1564; https://doi.org/10.3390/v14071564 - 19 Jul 2022
Viewed by 2142
Abstract
Crocodilepox virus (CRV) belongs to the Poxviridae family and mainly infects hatchling and juvenile Nile crocodiles. Most poxviruses encode inhibitors of the host antiviral protein kinase R (PKR), which is activated by viral double-stranded (ds) RNA formed during virus replication, resulting in the [...] Read more.
Crocodilepox virus (CRV) belongs to the Poxviridae family and mainly infects hatchling and juvenile Nile crocodiles. Most poxviruses encode inhibitors of the host antiviral protein kinase R (PKR), which is activated by viral double-stranded (ds) RNA formed during virus replication, resulting in the phosphorylation of eIF2α and the subsequent shutdown of general mRNA translation. Because CRV lacks orthologs of known poxviral PKR inhibitors, we experimentally characterized one candidate (CRV157), which contains a predicted dsRNA-binding domain. Bioinformatic analyses indicated that CRV157 evolved independently from other poxvirus PKR inhibitors. CRV157 bound to dsRNA, co-localized with PKR in the cytosol, and inhibited PKR from various species. To analyze whether CRV157 could inhibit PKR in the context of a poxvirus infection, we constructed recombinant vaccinia virus strains that contain either CRV157, or a mutant CRV157 deficient in dsRNA binding in a strain that lacks PKR inhibitors. The presence of wild-type CRV157 rescued vaccinia virus replication, while the CRV157 mutant did not. The ability of CRV157 to inhibit PKR correlated with virus replication and eIF2α phosphorylation. The independent evolution of CRV157 demonstrates that poxvirus PKR inhibitors evolved from a diverse set of ancestral genes in an example of convergent evolution. Full article
(This article belongs to the Special Issue Poxvirus)
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12 pages, 2127 KiB  
Article
Efficient Method for Generating Point Mutations in the Vaccinia Virus Genome Using CRISPR/Cas9
by Laetitia Boutin, Estelle Mosca and Frédéric Iseni
Viruses 2022, 14(7), 1559; https://doi.org/10.3390/v14071559 - 18 Jul 2022
Viewed by 1858
Abstract
The vaccinia virus (VACV) was previously used as a vaccine for smallpox eradication. Nowadays, recombinant VACVs are developed as vaccine platforms for infectious disease prevention and cancer treatment. The conventional method for genome editing of the VACV is based on homologous recombination, which [...] Read more.
The vaccinia virus (VACV) was previously used as a vaccine for smallpox eradication. Nowadays, recombinant VACVs are developed as vaccine platforms for infectious disease prevention and cancer treatment. The conventional method for genome editing of the VACV is based on homologous recombination, which is poorly efficient. Recently, the use of CRISPR/Cas9 technology was shown to greatly improve the speed and efficiency of the production of recombinant VACV expressing a heterologous gene. However, the ability to rapidly recover viruses bearing single nucleotide substitutions is still challenging. Notwithstanding, ongoing studies on the VACV and its interaction with the host cell could benefit from viral gene targeted mutagenesis. Here, we present a modified version of the CRISPR/Cas9 system for the rapid selection of mutant VACV carrying point mutations. For this purpose, we introduced a silent mutation into the donor gene (which will replace the wildtype gene) that serves a double function: it is located in the PAM (NGG) sequence, which is essential for Cas9 cleavage, and it alters a restriction site. This silent mutation, once introduced into the VACV genome, allows for rapid selection and screening of mutant viruses carrying a mutation of interest in the targeted gene. As a proof of concept, we produced several recombinant VACVs, with mutations in the E9L gene, upon which, phenotypic analysis was performed. Full article
(This article belongs to the Special Issue Poxvirus)
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13 pages, 5568 KiB  
Article
Enhancing the Immunogenicity of Vaccinia Virus
by Sergei N. Shchelkunov, Stanislav N. Yakubitskiy, Alexander A. Sergeev, Ekaterina V. Starostina, Ksenia A. Titova, Stepan A. Pyankov, Galina A. Shchelkunova, Mariya B. Borgoyakova, Alexey M. Zadorozhny, Lyubov A. Orlova, Denis N. Kisakov and Larisa I. Karpenko
Viruses 2022, 14(7), 1453; https://doi.org/10.3390/v14071453 - 30 Jun 2022
Cited by 4 | Viewed by 1682
Abstract
The conventional live smallpox vaccine based on the vaccinia virus (VACV) cannot be widely used today because it is highly reactogenic. Therefore, there is a demand for designing VACV variants possessing enhanced immunogenicity, making it possible to reduce the vaccine dose and, therefore, [...] Read more.
The conventional live smallpox vaccine based on the vaccinia virus (VACV) cannot be widely used today because it is highly reactogenic. Therefore, there is a demand for designing VACV variants possessing enhanced immunogenicity, making it possible to reduce the vaccine dose and, therefore, significantly eliminate the pathogenic effect of the VACV on the body. In this study, we analyzed the development of the humoral and T cell-mediated immune responses elicited by immunizing mice with low-dose VACV variants carrying the mutant A34R gene (which increases production of extracellular virions) or the deleted A35R gene (whose protein product inhibits antigen presentation by the major histocompatibility complex class II). The VACV LIVP strain, which is used as a smallpox vaccine in Russia, and its recombinant variants LIVP-A34R*, LIVP-dA35R, and LIVP-A34R*-dA35R, were compared upon intradermal immunization of BALB/c mice at a dose of 104 pfu/animal. The strongest T cell-mediated immunity was detected in mice infected with the LIVP-A34R*-dA35R virus. The parental LIVP strain induced a significantly lower antibody level compared to the strains carrying the modified A34R and A35R genes. Simultaneous modification of the A34R gene and deletion of the A35R gene in VACV LIVP synergistically enhanced the immunogenic properties of the LIVP-A34R*-dA35R virus. Full article
(This article belongs to the Special Issue Poxvirus)
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13 pages, 2838 KiB  
Article
New p35 (H3L) Epitope Involved in Vaccinia Virus Neutralization and Its Deimmunization
by Yana Khlusevich, Andrey Matveev, Lyudmila Emelyanova, Elena Goncharova, Natalia Golosova, Ivan Pereverzev and Nina Tikunova
Viruses 2022, 14(6), 1224; https://doi.org/10.3390/v14061224 - 05 Jun 2022
Cited by 6 | Viewed by 1989
Abstract
Vaccinia virus (VACV) is a promising oncolytic agent because it exhibits many characteristic features of an oncolytic virus. However, its effectiveness is limited by the strong antiviral immune response induced by this virus. One possible approach to overcome this limitation is to develop [...] Read more.
Vaccinia virus (VACV) is a promising oncolytic agent because it exhibits many characteristic features of an oncolytic virus. However, its effectiveness is limited by the strong antiviral immune response induced by this virus. One possible approach to overcome this limitation is to develop deimmunized recombinant VACV. It is known that VACV p35 is a major protein for B- and T-cell immune response. Despite the relevance of p35, its epitope structure remains insufficiently studied. To determine neutralizing epitopes, a panel of recombinant p35 variants was designed, expressed, and used for mice immunization. Plaque-reduction neutralization tests demonstrated that VACV was only neutralized by sera from mice that were immunized with variants containing both N- and C- terminal regions of p35. This result was confirmed by the depletion of anti-p35 mice sera with recombinant p35 variants. At least nine amino acid residues affecting the immunogenic profile of p35 were identified. Substitutions of seven residues led to disruption of B-cell epitopes, whereas substitutions of two residues resulted in the recognition of the mutant p35 solely by non-neutralizing antibodies. Full article
(This article belongs to the Special Issue Poxvirus)
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21 pages, 5506 KiB  
Article
Vaccinia Virus Arrests and Shifts the Cell Cycle
by Caroline K. Martin, Jerzy Samolej, Annabel T. Olson, Cosetta Bertoli, Matthew S. Wiebe, Robertus A. M. de Bruin and Jason Mercer
Viruses 2022, 14(2), 431; https://doi.org/10.3390/v14020431 - 19 Feb 2022
Cited by 2 | Viewed by 3050
Abstract
Modulation of the host cell cycle is a common strategy used by viruses to create a pro-replicative environment. To facilitate viral genome replication, vaccinia virus (VACV) has been reported to alter cell cycle regulation and trigger the host cell DNA damage response. However, [...] Read more.
Modulation of the host cell cycle is a common strategy used by viruses to create a pro-replicative environment. To facilitate viral genome replication, vaccinia virus (VACV) has been reported to alter cell cycle regulation and trigger the host cell DNA damage response. However, the cellular factors and viral effectors that mediate these changes remain unknown. Here, we set out to investigate the effect of VACV infection on cell proliferation and host cell cycle progression. Using a subset of VACV mutants, we characterise the stage of infection required for inhibition of cell proliferation and define the viral effectors required to dysregulate the host cell cycle. Consistent with previous studies, we show that VACV inhibits and subsequently shifts the host cell cycle. We demonstrate that these two phenomena are independent of one another, with viral early genes being responsible for cell cycle inhibition, and post-replicative viral gene(s) responsible for the cell cycle shift. Extending previous findings, we show that the viral kinase F10 is required to activate the DNA damage checkpoint and that the viral B1 kinase and/or B12 pseudokinase mediate degradation of checkpoint effectors p53 and p21 during infection. We conclude that VACV modulates host cell proliferation and host cell cycle progression through temporal expression of multiple VACV effector proteins. (209/200.) Full article
(This article belongs to the Special Issue Poxvirus)
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15 pages, 3483 KiB  
Article
Characterisation of an Anti-Vaccinia Virus F13 Single Chain Fragment Variable from a Human Anti-Vaccinia Virus-Specific Recombinant Immunoglobulin Library
by Henrike P. Ahsendorf, Ulrike S. Diesterbeck, Sven-Kevin Hotop, Michael Winkler, Mark Brönstrup and Claus-Peter Czerny
Viruses 2022, 14(2), 197; https://doi.org/10.3390/v14020197 - 20 Jan 2022
Cited by 1 | Viewed by 2021
Abstract
Vaccinia virus (VACV) belongs to the genus Orthopoxvirus of the family Poxviridae. There are four different forms of infectious virus particles: intracellular mature virus (IMV), intracellular en-veloped virus (IEV), cell-associated enveloped virus (CEV) and extracellular enveloped virus (EEV). The F13 protein occupies the [...] Read more.
Vaccinia virus (VACV) belongs to the genus Orthopoxvirus of the family Poxviridae. There are four different forms of infectious virus particles: intracellular mature virus (IMV), intracellular en-veloped virus (IEV), cell-associated enveloped virus (CEV) and extracellular enveloped virus (EEV). The F13 protein occupies the inner side of the CEV- and EEV-membranes and the outer side of the IEV-membranes. It plays an important role in wrapping progress and EEV production. We constructed a human single-chain fragment variable (scFv) library with a diversity of ≥4 × 108 independent colonies using peripheral blood from four vaccinated donors. One anti-F13 scFv was isolated and characterised after three rounds of panning. In Western blotting assays, the scFv 3E2 reacted with the recombinant F13VACV protein with a reduction of binding under denatured and reduced conditions. Two antigenic binding sites (139-GSIHTIKTLGVYSDY-153 and 169-AFNSAKNSWLNL-188) of scFv 3E2 were mapped using a cellulose membrane encompassing 372 15-mere peptides with 12 overlaps covering the whole F13 protein. No neutralisation capa-bilities were observed either in the presence or absence of complement. In conclusion, the con-struction of recombinant immunoglobulin libraries is a promising strategy to isolate specific scFvs to enable the study of the host-pathogen interaction. Full article
(This article belongs to the Special Issue Poxvirus)
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Review

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14 pages, 5560 KiB  
Review
Emergence of Salmon Gill Poxvirus
by Haitham Tartor, Maria K. Dahle, Snorre Gulla, Simon C. Weli and Mona C. Gjessing
Viruses 2022, 14(12), 2701; https://doi.org/10.3390/v14122701 - 01 Dec 2022
Viewed by 2545
Abstract
The Salmon gill poxvirus (SGPV) has emerged in recent years as the cause of an acute respiratory disease that can lead to high mortality in farmed Atlantic salmon presmolts, known as Salmon gill poxvirus disease. SGPV was first identified in Norway in the [...] Read more.
The Salmon gill poxvirus (SGPV) has emerged in recent years as the cause of an acute respiratory disease that can lead to high mortality in farmed Atlantic salmon presmolts, known as Salmon gill poxvirus disease. SGPV was first identified in Norway in the 1990s, and its large DNA genome, consisting of over 206 predicted protein-coding genes, was characterized in 2015. This review summarizes current knowledge relating to disease manifestation and its effects on the host immune system and describes dissemination of the virus. It also demonstrates how newly established molecular tools can help us to understand SGPV and its pathogenesis. Finally, we conclude and ask some burning questions that should be addressed in future research. Full article
(This article belongs to the Special Issue Poxvirus)
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