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Pathogens
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Poxviruses: Novel Concepts and Emerging Trends
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Poxviruses: Novel Concepts and Emerging Trends

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 30016

Special Issue Editor

Dr. Carlos Maluquer de Motes

E-Mail Website
Guest Editor
Department of Microbial Sciences, University of Surrey, Guildford GU2 7XH, UK
Interests: virology; virus-host interactions; viral immune evasion; poxviruses; innate immunity; immune recognition; interferons; nucleic acid sensing

Special Issue Information

Dear Colleagues,

All viruses need to infect, replicate, and transmit whilst they deal with host defensive processes. Poxviruses are evolutionarily successful viruses able to infect insects (entomopoxviruses) and chordates (chordopoxviruses), including fish, reptiles, aves, and mammals. To achieve this, poxviruses have evolved complex strategies to hijack cellular resources, subvert host antiviral responses, and produce multiple infectious forms adapted to cell-to-cell or host-to-host transmission. In some cases, this sophistication has led to narrow host range, sometimes restricted to one species, the most notorious of which was the human-specific variola virus that caused smallpox. Our knowledge on poxviruses has been driven by research on the prototypic member vaccinia virus, the smallpox vaccine, and a popular vaccine vector and oncolytic agent. However, many crucial insights into poxvirus biology and host antiviral defence have arisen from work with animal poxviruses like cowpox, ectromelia, and myxoma viruses. Over the last decade, transcriptomics and proteomics approaches have allowed us to uncover new details of how poxviruses enter cells, transcribe and translate their genetic information, and assemble new progeny viral particles. Equally, major breakthroughs have been reported on host sensing mechanisms and responses and poxvirus immune evasion strategies, with the implications these might have on the development of safer and more effective vaccines and oncolytics. In addition, deep-sequencing technologies are unravelling the genomes of novel poxvirus species, shedding light on the evolutionary history of the family and its strategies for adaptation. It is in this context of exciting discoveries and emerging concepts that Pathogens will launch a Special Issue on Poxviruses that aims to collect insightful reviews and perspectives on the biology of these unique viruses and their vast impact on human and animal medicine. Potential topics include but are not limited to molecular and cell biology of poxviruses; virus–host interactions; tropism; animal and human health; and biomedical applications.

I very much look forward to receiving your contributions for this exciting Issue.

Dr. Carlos Maluquer De Motes
Guest Editor

Manuscript Submission Information

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Keywords

  • poxviruses
  • entomopoxviruses
  • chordopoxviruses
  • vaccinia virus
  • variola virus
  • cowpox virus
  • ectromelia virus
  • monkeypox virus
  • smallpox vaccine
  • virus entry
  • virus replication
  • virus-host interactions
  • virus immune evasion
  • virus tropism
  • virus evolution
  • vaccine vectors
  • oncolytic agents

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Published Papers (6 papers)

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Research

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13 pages, 2077 KiB  
Article
Enhancing the Protective Immune Response to Administration of a LIVP-GFP Live Attenuated Vaccinia Virus to Mice
by Sergei N. Shchelkunov, Stanislav N. Yakubitskiy, Kseniya A. Titova, Stepan A. Pyankov and Alexander A. Sergeev
Pathogens 2021, 10(3), 377; https://doi.org/10.3390/pathogens10030377 - 21 Mar 2021
Cited by 1 | Viewed by 2528
Abstract
Following the WHO announcement of smallpox eradication, discontinuation of smallpox vaccination with vaccinia virus (VACV) was recommended. However, interest in VACV was soon renewed due to the opportunity of genetic engineering of the viral genome by directed insertion of foreign genes or introduction [...] Read more.
Following the WHO announcement of smallpox eradication, discontinuation of smallpox vaccination with vaccinia virus (VACV) was recommended. However, interest in VACV was soon renewed due to the opportunity of genetic engineering of the viral genome by directed insertion of foreign genes or introduction of mutations or deletions into selected viral genes. This genomic technology enabled production of stable attenuated VACV strains producing antigens of various infectious agents. Due to an increasing threat of human orthopoxvirus re-emergence, the development of safe highly immunogenic live orthopoxvirus vaccines using genetic engineering methods has been the challenge in recent years. In this study, we investigated an attenuated VACV LIVP-GFP (TK-) strain having an insertion of the green fluorescent protein gene into the viral thymidine kinase gene, which was generated on the basis of the LIVP (Lister-Institute for Viral Preparations) strain used in Russia as the first generation smallpox vaccine. We studied the effect of A34R gene modification and A35R gene deletion on the immunogenic and protective properties of the LIVP-GFP strain. The obtained data demonstrate that intradermal inoculation of the studied viruses induces higher production of VACV-specific antibodies compared to their levels after intranasal administration. Introduction of two point mutations into the A34R gene, which increase the yield of extracellular enveloped virions, and deletion of the A35R gene, the protein product of which inhibits presentation of antigens by MHC II, enhances protective potency of the created LIVP-TK--A34R*-dA35R virus against secondary lethal orthopoxvirus infection of BALB/c mice even at an intradermal dose as low as 103 plaque forming units (PFU)/mouse. This virus may be considered not only as a candidate attenuated live vaccine against smallpox and other human orthopoxvirus infections but also as a vector platform for development of safe multivalent live vaccines against other infectious diseases using genetic engineering methods. Full article
(This article belongs to the Special Issue Poxviruses: Novel Concepts and Emerging Trends)
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22 pages, 4947 KiB  
Article
First Insight into the Modulation of Noncanonical NF-κB Signaling Components by Poxviruses in Established Immune-Derived Cell Lines: An In Vitro Model of Ectromelia Virus Infection
by Justyna Struzik, Lidia Szulc-Dąbrowska, Matylda B. Mielcarska, Magdalena Bossowska-Nowicka, Michał Koper and Małgorzata Gieryńska
Pathogens 2020, 9(10), 814; https://doi.org/10.3390/pathogens9100814 - 4 Oct 2020
Cited by 1 | Viewed by 5222
Abstract
Dendritic cells (DCs) and macrophages are the first line of antiviral immunity. Viral pathogens exploit these cell populations for their efficient replication and dissemination via the modulation of intracellular signaling pathways. Disruption of the noncanonical nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) [...] Read more.
Dendritic cells (DCs) and macrophages are the first line of antiviral immunity. Viral pathogens exploit these cell populations for their efficient replication and dissemination via the modulation of intracellular signaling pathways. Disruption of the noncanonical nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling has frequently been observed in lymphoid cells upon infection with oncogenic viruses. However, several nononcogenic viruses have been shown to manipulate the noncanonical NF-κB signaling in different cell types. This study demonstrates the modulating effect of ectromelia virus (ECTV) on the components of the noncanonical NF-κB signaling pathway in established murine cell lines: JAWS II DCs and RAW 264.7 macrophages. ECTV affected the activation of TRAF2, cIAP1, RelB, and p100 upon cell treatment with both canonical and noncanonical NF-κB stimuli and thus impeded DNA binding by RelB and p52. ECTV also inhibited the expression of numerous genes related to the noncanonical NF-κB pathway and RelB-dependent gene expression in the cells treated with canonical and noncanonical NF-κB activators. Thus, our data strongly suggest that ECTV influenced the noncanonical NF-κB signaling components in the in vitro models. These findings provide new insights into the noncanonical NF-κB signaling components and their manipulation by poxviruses in vitro. Full article
(This article belongs to the Special Issue Poxviruses: Novel Concepts and Emerging Trends)
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Review

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17 pages, 1583 KiB  
Review
TNF Decoy Receptors Encoded by Poxviruses
by Francisco Javier Alvarez-de Miranda, Isabel Alonso-Sánchez, Antonio Alcamí and Bruno Hernaez
Pathogens 2021, 10(8), 1065; https://doi.org/10.3390/pathogens10081065 - 22 Aug 2021
Cited by 12 | Viewed by 4432
Abstract
Tumour necrosis factor (TNF) is an inflammatory cytokine produced in response to viral infections that promotes the recruitment and activation of leukocytes to sites of infection. This TNF-based host response is essential to limit virus spreading, thus poxviruses have evolutionarily adopted diverse molecular [...] Read more.
Tumour necrosis factor (TNF) is an inflammatory cytokine produced in response to viral infections that promotes the recruitment and activation of leukocytes to sites of infection. This TNF-based host response is essential to limit virus spreading, thus poxviruses have evolutionarily adopted diverse molecular mechanisms to counteract TNF antiviral action. These include the expression of poxvirus-encoded soluble receptors or proteins able to bind and neutralize TNF and other members of the TNF ligand superfamily, acting as decoy receptors. This article reviews in detail the various TNF decoy receptors identified to date in the genomes from different poxvirus species, with a special focus on their impact on poxvirus pathogenesis and their potential use as therapeutic molecules. Full article
(This article belongs to the Special Issue Poxviruses: Novel Concepts and Emerging Trends)
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17 pages, 862 KiB  
Review
Poxvirus Interactions with the Host Ubiquitin System
by Sian Lant and Carlos Maluquer de Motes
Pathogens 2021, 10(8), 1034; https://doi.org/10.3390/pathogens10081034 - 16 Aug 2021
Cited by 13 | Viewed by 3940
Abstract
The ubiquitin system has emerged as a master regulator of many, if not all, cellular functions. With its large repertoire of conjugating and ligating enzymes, the ubiquitin system holds a unique mechanism to provide selectivity and specificity in manipulating protein function. As intracellular [...] Read more.
The ubiquitin system has emerged as a master regulator of many, if not all, cellular functions. With its large repertoire of conjugating and ligating enzymes, the ubiquitin system holds a unique mechanism to provide selectivity and specificity in manipulating protein function. As intracellular parasites viruses have evolved to modulate the cellular environment to facilitate replication and subvert antiviral responses. Poxviruses are a large family of dsDNA viruses with large coding capacity that is used to synthetise proteins and enzymes needed for replication and morphogenesis as well as suppression of host responses. This review summarises our current knowledge on how poxvirus functions rely on the cellular ubiquitin system, and how poxviruses exploit this system to their own advantage, either facilitating uncoating and genome release and replication or rewiring ubiquitin ligases to downregulate critical antiviral factors. Whilst much remains to be known about the intricate interactions established between poxviruses and the host ubiquitin system, our knowledge has revealed crucial viral processes and important restriction factors that open novel avenues for antiviral treatment and provide fundamental insights on the biology of poxviruses and other virus families. Full article
(This article belongs to the Special Issue Poxviruses: Novel Concepts and Emerging Trends)
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24 pages, 2125 KiB  
Review
Poxviral Strategies to Overcome Host Cell Apoptosis
by Chathura D. Suraweera, Mark G. Hinds and Marc Kvansakul
Pathogens 2021, 10(1), 6; https://doi.org/10.3390/pathogens10010006 - 23 Dec 2020
Cited by 35 | Viewed by 3839
Abstract
Apoptosis is a form of cellular suicide initiated either via extracellular (extrinsic apoptosis) or intracellular (intrinsic apoptosis) cues. This form of programmed cell death plays a crucial role in development and tissue homeostasis in multicellular organisms and its dysregulation is an underlying cause [...] Read more.
Apoptosis is a form of cellular suicide initiated either via extracellular (extrinsic apoptosis) or intracellular (intrinsic apoptosis) cues. This form of programmed cell death plays a crucial role in development and tissue homeostasis in multicellular organisms and its dysregulation is an underlying cause for many diseases. Intrinsic apoptosis is regulated by members of the evolutionarily conserved B-cell lymphoma-2 (Bcl-2) family, a family that consists of pro- and anti-apoptotic members. Bcl-2 genes have also been assimilated by numerous viruses including pox viruses, in particular the sub-family of chordopoxviridae, a group of viruses known to infect almost all vertebrates. The viral Bcl-2 proteins are virulence factors and aid the evasion of host immune defenses by mimicking the activity of their cellular counterparts. Viral Bcl-2 genes have proved essential for the survival of virus infected cells and structural studies have shown that though they often share very little sequence identity with their cellular counterparts, they have near-identical 3D structures. However, their mechanisms of action are varied. In this review, we examine the structural biology, molecular interactions, and detailed mechanism of action of poxvirus encoded apoptosis inhibitors and how they impact on host–virus interactions to ultimately enable successful infection and propagation of viral infections. Full article
(This article belongs to the Special Issue Poxviruses: Novel Concepts and Emerging Trends)
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23 pages, 1193 KiB  
Review
Vaccinia Virus as a Master of Host Shutoff Induction: Targeting Processes of the Central Dogma and Beyond
by Pragyesh Dhungel, Fernando M. Cantu, Joshua A. Molina and Zhilong Yang
Pathogens 2020, 9(5), 400; https://doi.org/10.3390/pathogens9050400 - 21 May 2020
Cited by 20 | Viewed by 8874
Abstract
The synthesis of host cell proteins is adversely inhibited in many virus infections, whereas viral proteins are efficiently synthesized. This phenomenon leads to the accumulation of viral proteins concurrently with a profound decline in global host protein synthesis, a phenomenon often termed “host [...] Read more.
The synthesis of host cell proteins is adversely inhibited in many virus infections, whereas viral proteins are efficiently synthesized. This phenomenon leads to the accumulation of viral proteins concurrently with a profound decline in global host protein synthesis, a phenomenon often termed “host shutoff”. To induce host shutoff, a virus may target various steps of gene expression, as well as pre- and post-gene expression processes. During infection, vaccinia virus (VACV), the prototype poxvirus, targets all major processes of the central dogma of genetics, as well as pre-transcription and post-translation steps to hinder host cell protein production. In this article, we review the strategies used by VACV to induce host shutoff in the context of strategies employed by other viruses. We elaborate on how VACV induces host shutoff by targeting host cell DNA synthesis, RNA production and processing, mRNA translation, and protein degradation. We emphasize the topics on VACV’s approaches toward modulating mRNA processing, stability, and translation during infection. Finally, we propose avenues for future investigations, which will facilitate our understanding of poxvirus biology, as well as fundamental cellular gene expression and regulation mechanisms. Full article
(This article belongs to the Special Issue Poxviruses: Novel Concepts and Emerging Trends)
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