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Pathogens
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Poxvirus-Driven Insights into Virus and Host Biology
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Poxvirus-Driven Insights into Virus and Host Biology

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

Deadline for manuscript submissions: closed (15 January 2023) | Viewed by 22054

Special Issue Editors

Prof. Dr. Stefan Rothenburg

E-Mail Website
Guest Editor
Department of Medical Microbiology and Immunology, Davis School of Medicine, University of California, Davis, CA 95616-5271, USA
Interests: poxviruses; host–virus interactions; evolution; translational control; PKR
Dr. Greg Brennan

E-Mail Website
Guest Editor
Department of Medical Microbiology and Immunology, Davis School of Medicine, University of California, Davis, CA 95616-5271, USA
Interests: poxviruses; host–virus interactions; evolution; translational control; PKR

Special Issue Information

Dear Colleagues,

Poxviruses are a diverse family of DNA viruses that can infect both vertebrates and arthropods. They have been responsible for some of the deadliest pandemics of the past, and some species remain substantial threats to both human and animal health. This threat arises in part because poxviruses fill a variety of ecological niches, from viruses that infect a single species, e.g., molluscum contagiosum, to viruses with the ability to infect an astonishingly broad range of hosts, e.g., cowpox virus. Poxviruses have been instrumental in gaining fundamental insights into basic molecular biology, host–virus interactions, and evolution. This understating of host and virus biology has enabled the use of poxviruses for therapeutic purposes, including cancer therapy and vaccine vectors. This Special Issue on poxviruses will provide a comprehensive overview of basic and translational advances in the field in the form of review and original research articles on topics including but not limited to basic poxvirus biology, host–virus interactions, host range, mechanisms of viral evolution, poxvirus-vectored therapeutic approaches, and characterization of novel poxviruses.

Dr. Stefan Rothenburg
Dr. Greg Brennan
Guest Editors

Manuscript Submission Information

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Keywords

  • poxvirus biology
  • host–virus interactions
  • host range
  • mechanisms of viral evolution
  • poxvirus-vectored therapeutic approaches
  • characterization of novel poxviruses

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Published Papers (7 papers)

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Research

Jump to: Review

14 pages, 2465 KiB  
Article
Generation of Multiple Arbovirus-like Particles Using a Rapid Recombinant Vaccinia Virus Expression Platform
by Yuxiang Wang, Anthony Griffiths, Douglas E. Brackney and Paulo H. Verardi
Pathogens 2022, 11(12), 1505; https://doi.org/10.3390/pathogens11121505 - 9 Dec 2022
Cited by 3 | Viewed by 2546
Abstract
As demonstrated by the 2015 Zika virus outbreak in the Americas, emerging and re-emerging arboviruses are public health threats that warrant research investment for the development of effective prophylactics and therapeutics. Many arboviral diseases are underreported, neglected, or of low prevalence, yet they [...] Read more.
As demonstrated by the 2015 Zika virus outbreak in the Americas, emerging and re-emerging arboviruses are public health threats that warrant research investment for the development of effective prophylactics and therapeutics. Many arboviral diseases are underreported, neglected, or of low prevalence, yet they all have the potential to cause outbreaks of local and international concern. Here, we show the production of virus-like particles (VLPs) using a rapid and efficient recombinant vaccinia virus (VACV) expression system for five tick- and mosquito-borne arboviruses: Powassan virus (POWV), Heartland virus (HRTV), severe fever with thrombocytopenia syndrome virus (SFTSV), Bourbon virus (BRBV) and Mayaro virus (MAYV). We detected the expression of arbovirus genes of interest by Western blot and observed the expression of VLPs that resemble native virions under transmission electron microscopy. We were also able to improve the secretion of POWV VLPs by modifying the signal sequence within the capsid gene. This study describes the use of a rapid VACV platform for the production and purification of arbovirus VLPs that can be used as subunit or vectored vaccines, and provides insights into the selection of arbovirus genes for VLP formation and genetic modifications to improve VLP secretion and yield. Full article
(This article belongs to the Special Issue Poxvirus-Driven Insights into Virus and Host Biology)
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25 pages, 2787 KiB  
Article
Strategies and Patterns of Codon Bias in Molluscum Contagiosum Virus
by Rahul Raveendran Nair, Manikandan Mohan, Gudepalya R. Rudramurthy, Reethu Vivekanandam and Panayampalli S. Satheshkumar
Pathogens 2021, 10(12), 1649; https://doi.org/10.3390/pathogens10121649 - 20 Dec 2021
Cited by 3 | Viewed by 3109
Abstract
Trends associated with codon usage in molluscum contagiosum virus (MCV) and factors governing the evolution of codon usage have not been investigated so far. In this study, attempts were made to decipher the codon usage trends and discover the major evolutionary forces that [...] Read more.
Trends associated with codon usage in molluscum contagiosum virus (MCV) and factors governing the evolution of codon usage have not been investigated so far. In this study, attempts were made to decipher the codon usage trends and discover the major evolutionary forces that influence the patterns of codon usage in MCV with special reference to sub-types 1 and 2, MCV-1 and MCV-2, respectively. Three hypotheses were tested: (1) codon usage patterns of MCV-1 and MCV-2 are identical; (2) SCUB (synonymous codon usage bias) patterns of MCV-1 and MCV-2 slightly deviate from that of human host to avoid affecting the fitness of host; and (3) translational selection predominantly shapes the SCUB of MCV-1 and MCV-2. Various codon usage indices viz. relative codon usage value, effective number of codons and codon adaptation index were calculated to infer the nature of codon usage. Correspondence analysis and correlation analysis were performed to assess the relative contribution of silent base contents and significance of codon usage indices in defining bias in codon usage. Among the tested hypotheses, only the second and third hypotheses were accepted. Full article
(This article belongs to the Special Issue Poxvirus-Driven Insights into Virus and Host Biology)
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Review

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20 pages, 1538 KiB  
Review
How to Inhibit Nuclear Factor-Kappa B Signaling: Lessons from Poxviruses
by Joshua B. Reus, Emily A. Rex and Don B. Gammon
Pathogens 2022, 11(9), 1061; https://doi.org/10.3390/pathogens11091061 - 18 Sep 2022
Cited by 7 | Viewed by 2334
Abstract
The Nuclear Factor-kappa B (NF-κB) family of transcription factors regulates key host inflammatory and antiviral gene expression programs, and thus, is often activated during viral infection through the action of pattern-recognition receptors and cytokine–receptor interactions. In turn, many viral pathogens encode strategies to [...] Read more.
The Nuclear Factor-kappa B (NF-κB) family of transcription factors regulates key host inflammatory and antiviral gene expression programs, and thus, is often activated during viral infection through the action of pattern-recognition receptors and cytokine–receptor interactions. In turn, many viral pathogens encode strategies to manipulate and/or inhibit NF-κB signaling. This is particularly exemplified by vaccinia virus (VV), the prototypic poxvirus, which encodes at least 18 different inhibitors of NF-κB signaling. While many of these poxviral NF-κB inhibitors are not required for VV replication in cell culture, they virtually all modulate VV virulence in animal models, underscoring the important influence of poxvirus–NF-κB pathway interactions on viral pathogenesis. Here, we review the diversity of mechanisms through which VV-encoded antagonists inhibit initial NF-κB pathway activation and NF-κB signaling intermediates, as well as the activation and function of NF-κB transcription factor complexes. Full article
(This article belongs to the Special Issue Poxvirus-Driven Insights into Virus and Host Biology)
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26 pages, 2683 KiB  
Review
Poxvirus Recombination
by David Hugh Evans
Pathogens 2022, 11(8), 896; https://doi.org/10.3390/pathogens11080896 - 9 Aug 2022
Cited by 13 | Viewed by 3636
Abstract
Genetic recombination is used as a tool for modifying the composition of poxvirus genomes in both discovery and applied research. This review documents the history behind the development of these tools as well as what has been learned about the processes that catalyze [...] Read more.
Genetic recombination is used as a tool for modifying the composition of poxvirus genomes in both discovery and applied research. This review documents the history behind the development of these tools as well as what has been learned about the processes that catalyze virus recombination and the links between it and DNA replication and repair. The study of poxvirus recombination extends back to the 1930s with the discovery that one virus can reactivate another by a process later shown to generate recombinants. In the years that followed it was shown that recombinants can be produced in virus-by-virus crosses within a genus (e.g., variola-by-rabbitpox) and efforts were made to produce recombination-based genetic maps with modest success. The marker rescue mapping method proved more useful and led to methods for making genetically engineered viruses. Many further insights into the mechanism of recombination have been provided by transfection studies which have shown that this is a high-frequency process associated with hybrid DNA formation and inextricably linked to replication. The links reflect the fact that poxvirus DNA polymerases, specifically the vaccinia virus E9 enzyme, can catalyze strand transfer in in vivo and in vitro reactions dependent on the 3′-to-5′ proofreading exonuclease and enhanced by the I3 replicative single-strand DNA binding protein. These reactions have shaped the composition of virus genomes and are modulated by constraints imposed on virus–virus interactions by viral replication in cytoplasmic factories. As recombination reactions are used for replication fork assembly and repair in many biological systems, further study of these reactions may provide new insights into still poorly understood features of poxvirus DNA replication. Full article
(This article belongs to the Special Issue Poxvirus-Driven Insights into Virus and Host Biology)
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22 pages, 430 KiB  
Review
Comparative Pathology of Zoonotic Orthopoxviruses
by Amy L. MacNeill
Pathogens 2022, 11(8), 892; https://doi.org/10.3390/pathogens11080892 - 9 Aug 2022
Cited by 21 | Viewed by 3843
Abstract
This review provides a brief history of the impacts that a human-specific Orthopoxvirus (OPXV), Variola virus, had on mankind, recalls how critical vaccination was for the eradication of this disease, and discusses the consequences of discontinuing vaccination against OPXV. One of these [...] Read more.
This review provides a brief history of the impacts that a human-specific Orthopoxvirus (OPXV), Variola virus, had on mankind, recalls how critical vaccination was for the eradication of this disease, and discusses the consequences of discontinuing vaccination against OPXV. One of these consequences is the emergence of zoonotic OPXV diseases, including Monkeypox virus (MPXV). The focus of this manuscript is to compare pathology associated with zoonotic OPXV infection in veterinary species and in humans. Efficient recognition of poxvirus lesions and other, more subtle signs of disease in multiple species is critical to prevent further spread of poxvirus infections. Additionally included are a synopsis of the pathology observed in animal models of MPXV infection, the recent spread of MPXV among humans, and a discussion of the potential for this virus to persist in Europe and the Americas. Full article
(This article belongs to the Special Issue Poxvirus-Driven Insights into Virus and Host Biology)
18 pages, 2906 KiB  
Review
Poxviral ANKR/F-box Proteins: Substrate Adapters for Ubiquitylation and More
by Robert J. Ingham, Farynna Loubich Facundo and Jianing Dong
Pathogens 2022, 11(8), 875; https://doi.org/10.3390/pathogens11080875 - 3 Aug 2022
Cited by 9 | Viewed by 2654
Abstract
Poxviruses are double-stranded DNA viruses that infect insects and a variety of vertebrate species. The large genomes of poxviruses contain numerous genes that allow these viruses to successfully establish infection, including those that help evade the host immune response and prevent cell death. [...] Read more.
Poxviruses are double-stranded DNA viruses that infect insects and a variety of vertebrate species. The large genomes of poxviruses contain numerous genes that allow these viruses to successfully establish infection, including those that help evade the host immune response and prevent cell death. Ankyrin-repeat (ANKR)/F-box proteins are almost exclusively found in poxviruses, and they function as substrate adapters for Skp1-Cullin-1-F-box protein (SCF) multi-subunit E3 ubiquitin (Ub)-ligases. In this regard, they use their C-terminal F-box domain to bind Skp1, Cullin-1, and Roc1 to recruit cellular E2 enzymes to facilitate the ubiquitylation, and subsequent proteasomal degradation, of proteins bound to their N-terminal ANKRs. However, these proteins do not just function as substrate adapters as they also have Ub-independent activities. In this review, we examine both Ub-dependent and -independent activities of ANKR/F-box proteins and discuss how poxviruses use these proteins to counteract the host innate immune response, uncoat their genome, replicate, block cell death, and influence transcription. Finally, we consider important outstanding questions that need to be answered in order to better understand the function of this versatile protein family. Full article
(This article belongs to the Special Issue Poxvirus-Driven Insights into Virus and Host Biology)
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13 pages, 3247 KiB  
Review
Antagonism of Protein Kinase R by Large DNA Viruses
by Annabel T. Olson, Stephanie J. Child and Adam P. Geballe
Pathogens 2022, 11(7), 790; https://doi.org/10.3390/pathogens11070790 - 12 Jul 2022
Cited by 2 | Viewed by 2611
Abstract
Decades of research on vaccinia virus (VACV) have provided a wealth of insights and tools that have proven to be invaluable in a broad range of studies of molecular virology and pathogenesis. Among the challenges that viruses face are intrinsic host cellular defenses, [...] Read more.
Decades of research on vaccinia virus (VACV) have provided a wealth of insights and tools that have proven to be invaluable in a broad range of studies of molecular virology and pathogenesis. Among the challenges that viruses face are intrinsic host cellular defenses, such as the protein kinase R pathway, which shuts off protein synthesis in response to the dsRNA that accumulates during replication of many viruses. Activation of PKR results in phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α), inhibition of protein synthesis, and limited viral replication. VACV encodes two well-characterized antagonists, E3L and K3L, that can block the PKR pathway and thus enable the virus to replicate efficiently. The use of VACV with a deletion of the dominant factor, E3L, enabled the initial identification of PKR antagonists encoded by human cytomegalovirus (HCMV), a prevalent and medically important virus. Understanding the molecular mechanisms of E3L and K3L function facilitated the dissection of the domains, species-specificity, and evolutionary potential of PKR antagonists encoded by human and nonhuman CMVs. While remaining cognizant of the substantial differences in the molecular virology and replication strategies of VACV and CMVs, this review illustrates how VACV can provide a valuable guide for the study of other experimentally less tractable viruses. Full article
(This article belongs to the Special Issue Poxvirus-Driven Insights into Virus and Host Biology)
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