Special Issue "Poxvirus Evolution"

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

Deadline for manuscript submissions: closed (28 February 2015).

Special Issue Editors

Dr. Elliot J. Lefkowitz
Website
Guest Editor
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35222, USA
Interests: microbial genomics and evolution; poxvirus evolution; virus taxonomy; bioinformatics; biomedical informatics
Dr. Chris Upton
Website
Guest Editor
Department of Biochemistry and Microbiology, The University of Victoria, Petch Bldg Rm 213, 3800 Finnerty Road, Victoria BC V8P 5C2, Canada
Interests: poxviruses; viral genomics and evolution; bioinformatics software development; virus virulence mechanisms

Special Issue Information

Dear Colleagues,

Since 1990, with the release of the Vaccinia-Copenhagen genome sequence, there has been a continuous and slowly increasing stream of genomic information available for members of the virus family, Poxviridae. In this Special Issue of Viruses, we hope to collect a series of articles and reviews that will highlight what we have learned from all these A, C, G and Ts—a current picture of the poxviruses, from an evolutionary standpoint. Although poxviruses are now in the intermediate size category for viruses, the puzzles around poxvirus evolution are clearly still large. These include the relationship of poxviruses to other viruses, the transfer of genes between poxvirus and host genomes, the evolution of widely disparate A+T% content in poxvirus genomes, the generation of multigene families, virus speciation events, changes to virus host range, evolution of poxvirus promoter classes, and the extent to which recombination has shaped poxvirus genome sequences. Answers to these questions do not merely provide information on poxvirus evolution as a lesson in history, but also focus on contemporary and future problems. For example, what is the likelihood that monkeypox, or some other poxvirus species, might evolve to become a new smallpox-like human disease? Or how can our understanding of virus host range adaptation be used to support the development of better vaccines or anti-cancer therapeutics? Especially important, as the destruction of the remaining stocks of variola virus continues to be debated, is the extent to which data derived from genome sequences and bioinformatics analysis can be used to answer remaining questions concerning smallpox biology? Our goal for this Special Issue is a compendium that reflects our current understanding of poxvirus evolution in a broad sense. We hope this information will support reconstruction of the evolutionary history of poxvirus species, enhance our current understanding of poxvirus biology, and help the research community make intelligent predictions of the possible evolutionary paths that these viruses might take.

Dr. Elliot J. Lefkowitz
Dr. Chris Upton
Guest Editors

Manuscript Submission Information

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Keywords

  • poxviruses
  • virus evolution
  • virus genomics

Published Papers (10 papers)

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Research

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Open AccessArticle
A Phylogeographic Investigation of African Monkeypox
Viruses 2015, 7(4), 2168-2184; https://doi.org/10.3390/v7042168 - 22 Apr 2015
Cited by 11
Abstract
Monkeypox is a zoonotic disease caused by a virus member of the genus Orthopoxvirus and is endemic to Central and Western African countries. Previous work has identified two geographically disjuct clades of monkeypox virus based on the analysis of a few genomes coupled [...] Read more.
Monkeypox is a zoonotic disease caused by a virus member of the genus Orthopoxvirus and is endemic to Central and Western African countries. Previous work has identified two geographically disjuct clades of monkeypox virus based on the analysis of a few genomes coupled with epidemiological and clinical analyses; however, environmental and geographic causes of this differentiation have not been explored. Here, we expand previous phylogenetic studies by analyzing a larger set of monkeypox virus genomes originating throughout Sub-Saharan Africa to identify possible biogeographic barriers associated with genetic differentiation; and projected ecological niche models onto environmental conditions at three periods in the past to explore the potential role of climate oscillations in the evolution of the two primary clades. Analyses supported the separation of the Congo Basin and West Africa clades; the Congo Basin clade shows much shorter branches, which likely indicate a more recent diversification of isolates within this clade. The area between the Sanaga and Cross Rivers divides the two clades and the Dahomey Gap seems to have also served as a barrier within the West African clade. Contraction of areas with suitable environments for monkeypox virus during the Last Glacial Maximum, suggests that the Congo Basin clade of monkeypox virus experienced a severe bottleneck and has since expanded its geographic range. Full article
(This article belongs to the Special Issue Poxvirus Evolution)
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Open AccessArticle
Genome Variability and Gene Content in Chordopoxviruses: Dependence on Microsatellites
Viruses 2015, 7(4), 2126-2146; https://doi.org/10.3390/v7042126 - 22 Apr 2015
Cited by 6
Abstract
To investigate gene loss in poxviruses belonging to the Chordopoxvirinae subfamily, we assessed the gene content of representative members of the subfamily, and determined whether individual genes present in each genome were intact, truncated, or fragmented. When nonintact genes were identified, the early [...] Read more.
To investigate gene loss in poxviruses belonging to the Chordopoxvirinae subfamily, we assessed the gene content of representative members of the subfamily, and determined whether individual genes present in each genome were intact, truncated, or fragmented. When nonintact genes were identified, the early stop mutations (ESMs) leading to gene truncation or fragmentation were analyzed. Of all the ESMs present in these poxvirus genomes, over 65% co-localized with microsatellites—simple sequence nucleotide repeats. On average, microsatellites comprise 24% of the nucleotide sequence of these poxvirus genomes. These simple repeats have been shown to exhibit high rates of variation, and represent a target for poxvirus protein variation, gene truncation, and reductive evolution. Full article
(This article belongs to the Special Issue Poxvirus Evolution)
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Open AccessArticle
Gene Acquisition Convergence between Entomopoxviruses and Baculoviruses
Viruses 2015, 7(4), 1960-1974; https://doi.org/10.3390/v7041960 - 13 Apr 2015
Cited by 28
Abstract
Organisms from diverse phylogenetic origins can thrive within the same ecological niches. They might be induced to evolve convergent adaptations in response to a similar landscape of selective pressures. Their genomes should bear the signature of this process. The study of unrelated virus [...] Read more.
Organisms from diverse phylogenetic origins can thrive within the same ecological niches. They might be induced to evolve convergent adaptations in response to a similar landscape of selective pressures. Their genomes should bear the signature of this process. The study of unrelated virus lineages infecting the same host panels guarantees a clear identification of phyletically independent convergent adaptation. Here, we investigate the evolutionary history of genes in the accessory genome shared by unrelated insect large dsDNA viruses: the entomopoxviruses (EPVs, Poxviridae) and the baculoviruses (BVs). EPVs and BVs have overlapping ecological niches and have independently evolved similar infection processes. They are, in theory, subjected to the same selective pressures from their host’s immune responses. Their accessory genomes might, therefore, bear analogous genomic signatures of convergent adaption and could point out key genomic mechanisms of adaptation hitherto undetected in viruses. We uncovered 32 homologous, yet independent acquisitions of genes originating from insect hosts, different eukaryotes, bacteria and viruses. We showed different evolutionary levels of gene acquisition convergence in these viruses, underlining a continuous evolutionary process. We found both recent and ancient gene acquisitions possibly involved to the adaptation to both specific and distantly related hosts. Multidirectional and multipartite gene exchange networks appear to constantly drive exogenous gene assimilations, bringing key adaptive innovations and shaping the life histories of large DNA viruses. This evolutionary process might lead to genome level adaptive convergence. Full article
(This article belongs to the Special Issue Poxvirus Evolution)
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Open AccessArticle
From Lesions to Viral Clones: Biological and Molecular Diversity amongst Autochthonous Brazilian Vaccinia Virus
Viruses 2015, 7(3), 1218-1237; https://doi.org/10.3390/v7031218 - 16 Mar 2015
Cited by 11
Abstract
Vaccinia virus (VACV) has had an important role for humanity because of its use during the smallpox eradication campaign. VACV is the etiologic agent of the bovine vaccinia (BV), an emerging zoonosis that has been associated with economic, social, veterinary and public health [...] Read more.
Vaccinia virus (VACV) has had an important role for humanity because of its use during the smallpox eradication campaign. VACV is the etiologic agent of the bovine vaccinia (BV), an emerging zoonosis that has been associated with economic, social, veterinary and public health problems, mainly in Brazil and India. Despite the current and historical VACV importance, there is little information about its circulation, prevalence, origins and maintenance in the environment, natural reservoirs and diversity. Brazilian VACV (VACV-BR) are grouped into at least two groups based on genetic and biological diversity: group 1 (G1) and group 2 (G2). In this study, we went to the field and investigated VACV clonal diversity directly from exanthemous lesions, during BV outbreaks. Our results demonstrate that the G1 VACV-BR were more frequently isolated. Furthermore, we were able to co-detect the two variants (G1 and G2) in the same sample. Molecular and biological analysis corroborated previous reports and confirmed the co-circulation of two VACV-BR lineages. The detected G2 clones presented exclusive genetic and biological markers, distinct to reference isolates, including VACV-Western Reserve. Two clones presented a mosaic profile, with both G1 and G2 features based on the molecular analysis of A56R, A26L and C23L genes. Indeed, some SNPs and INDELs in A56R nucleotide sequences were observed among clones of the same virus population, maybe as a result of an increased mutation rate in a mixed population. These results provide information about the diversity profile in VACV populations, highlighting its importance to VACV evolution and maintenance in the environment. Full article
(This article belongs to the Special Issue Poxvirus Evolution)
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Review

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Open AccessReview
Structural Conservation and Functional Diversity of the Poxvirus Immune Evasion (PIE) Domain Superfamily
Viruses 2015, 7(9), 4873-4893; https://doi.org/10.3390/v7092848 - 28 Aug 2015
Cited by 19
Abstract
Poxviruses encode a broad array of proteins that serve to undermine host immune defenses. Structural analysis of four of these seemingly unrelated proteins revealed the recurrent use of a conserved beta-sandwich fold that has not been observed in any eukaryotic or prokaryotic protein. [...] Read more.
Poxviruses encode a broad array of proteins that serve to undermine host immune defenses. Structural analysis of four of these seemingly unrelated proteins revealed the recurrent use of a conserved beta-sandwich fold that has not been observed in any eukaryotic or prokaryotic protein. Herein we propose to call this unique structural scaffolding the PIE (Poxvirus Immune Evasion) domain. PIE domain containing proteins are abundant in chordopoxvirinae, with our analysis identifying 20 likely PIE subfamilies among 33 representative genomes spanning 7 genera. For example, cowpox strain Brighton Red appears to encode 10 different PIEs: vCCI, A41, C8, M2, T4 (CPVX203), and the SECRET proteins CrmB, CrmD, SCP-1, SCP-2, and SCP-3. Characterized PIE proteins all appear to be nonessential for virus replication, and all contain signal peptides for targeting to the secretory pathway. The PIE subfamilies differ primarily in the number, size, and location of structural embellishments to the beta-sandwich core that confer unique functional specificities. Reported ligands include chemokines, GM-CSF, IL-2, MHC class I, and glycosaminoglycans. We expect that the list of ligands and receptors engaged by the PIE domain will grow as we come to better understand how this versatile structural architecture can be tailored to manipulate host responses to infection. Full article
(This article belongs to the Special Issue Poxvirus Evolution)
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Open AccessReview
The Evolution of Poxvirus Vaccines
Viruses 2015, 7(4), 1726-1803; https://doi.org/10.3390/v7041726 - 07 Apr 2015
Cited by 71
Abstract
After Edward Jenner established human vaccination over 200 years ago, attenuated poxviruses became key players to contain the deadliest virus of its own family: Variola virus (VARV), the causative agent of smallpox. Cowpox virus (CPXV) and horsepox virus (HSPV) were extensively used to [...] Read more.
After Edward Jenner established human vaccination over 200 years ago, attenuated poxviruses became key players to contain the deadliest virus of its own family: Variola virus (VARV), the causative agent of smallpox. Cowpox virus (CPXV) and horsepox virus (HSPV) were extensively used to this end, passaged in cattle and humans until the appearance of vaccinia virus (VACV), which was used in the final campaigns aimed to eradicate the disease, an endeavor that was accomplished by the World Health Organization (WHO) in 1980. Ever since, naturally evolved strains used for vaccination were introduced into research laboratories where VACV and other poxviruses with improved safety profiles were generated. Recombinant DNA technology along with the DNA genome features of this virus family allowed the generation of vaccines against heterologous diseases, and the specific insertion and deletion of poxvirus genes generated an even broader spectrum of modified viruses with new properties that increase their immunogenicity and safety profile as vaccine vectors. In this review, we highlight the evolution of poxvirus vaccines, from first generation to the current status, pointing out how different vaccines have emerged and approaches that are being followed up in the development of more rational vaccines against a wide range of diseases. Full article
(This article belongs to the Special Issue Poxvirus Evolution)
Open AccessReview
Molecular Genetic Analysis of Orf Virus: A Poxvirus That Has Adapted to Skin
Viruses 2015, 7(3), 1505-1539; https://doi.org/10.3390/v7031505 - 23 Mar 2015
Cited by 54
Abstract
Orf virus is the type species of the Parapoxvirus genus of the family Poxviridae. It induces acute pustular skin lesions in sheep and goats and is transmissible to humans. The genome is G+C rich, 138 kbp and encodes 132 genes. It shares [...] Read more.
Orf virus is the type species of the Parapoxvirus genus of the family Poxviridae. It induces acute pustular skin lesions in sheep and goats and is transmissible to humans. The genome is G+C rich, 138 kbp and encodes 132 genes. It shares many essential genes with vaccinia virus that are required for survival but encodes a number of unique factors that allow it to replicate in the highly specific immune environment of skin. Phylogenetic analysis suggests that both viral interleukin-10 and vascular endothelial growth factor genes have been “captured” from their host during the evolution of the parapoxviruses. Genes such as a chemokine binding protein and a protein that binds granulocyte-macrophage colony-stimulating factor and interleukin-2 appear to have evolved from a common poxvirus ancestral gene while three parapoxvirus nuclear factor (NF)-κB signalling pathway inhibitors have no homology to other known NF-κB inhibitors. A homologue of an anaphase-promoting complex subunit that is believed to manipulate the cell cycle and enhance viral DNA synthesis appears to be a specific adaptation for viral-replication in keratinocytes. The review focuses on the unique genes of orf virus, discusses their evolutionary origins and their role in allowing viral-replication in the skin epidermis. Full article
(This article belongs to the Special Issue Poxvirus Evolution)
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Open AccessReview
The Origin of the Variola Virus
Viruses 2015, 7(3), 1100-1112; https://doi.org/10.3390/v7031100 - 10 Mar 2015
Cited by 19
Abstract
The question of the origin of smallpox, one of the major menaces to humankind, is a constant concern for the scientific community. Smallpox is caused by the agent referred to as the variola virus (VARV), which belongs to the genus Orthopoxvirus. In [...] Read more.
The question of the origin of smallpox, one of the major menaces to humankind, is a constant concern for the scientific community. Smallpox is caused by the agent referred to as the variola virus (VARV), which belongs to the genus Orthopoxvirus. In the last century, smallpox was declared eradicated from the human community; however, the mechanisms responsible for the emergence of new dangerous pathogens have yet to be unraveled. Evolutionary analyses of the molecular biological genomic data of various orthopoxviruses, involving a wide range of epidemiological and historical information about smallpox, have made it possible to date the emergence of VARV. Comparisons of the VARV genome to the genomes of the most closely related orthopoxviruses and the examination of the distribution their natural hosts’ ranges suggest that VARV emerged 3000 to 4000 years ago in the east of the African continent. The VARV evolution rate has been estimated to be approximately 2 × 10−6 substitutions/site/year for the central conserved genomic region and 4 × 10−6 substitutions/site/year for the synonymous substitutions in the genome. Presumably, the introduction of camels to Africa and the concurrent changes to the climate were the particular factors that triggered the divergent evolution of a cowpox-like ancestral virus and thereby led to the emergence of VARV. Full article
(This article belongs to the Special Issue Poxvirus Evolution)
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Open AccessReview
Myxoma Virus and the Leporipoxviruses: An Evolutionary Paradigm
Viruses 2015, 7(3), 1020-1061; https://doi.org/10.3390/v7031020 - 06 Mar 2015
Cited by 41
Abstract
Myxoma virus (MYXV) is the type species of the Leporipoxviruses, a genus of Chordopoxvirinae, double stranded DNA viruses, whose members infect leporids and squirrels, inducing cutaneous fibromas from which virus is mechanically transmitted by biting arthropods. However, in the European rabbit [...] Read more.
Myxoma virus (MYXV) is the type species of the Leporipoxviruses, a genus of Chordopoxvirinae, double stranded DNA viruses, whose members infect leporids and squirrels, inducing cutaneous fibromas from which virus is mechanically transmitted by biting arthropods. However, in the European rabbit (Oryctolagus cuniculus), MYXV causes the lethal disease myxomatosis. The release of MYXV as a biological control for the wild European rabbit population in Australia, initiated one of the great experiments in evolution. The subsequent coevolution of MYXV and rabbits is a classic example of natural selection acting on virulence as a pathogen adapts to a novel host species. Slightly attenuated mutants of the progenitor virus were more readily transmitted by the mosquito vector because the infected rabbit survived longer, while highly attenuated viruses could be controlled by the rabbit immune response. As a consequence, moderately attenuated viruses came to dominate. This evolution of the virus was accompanied by selection for genetic resistance in the wild rabbit population, which may have created an ongoing co-evolutionary dynamic between resistance and virulence for efficient transmission. This natural experiment was repeated on a continental scale with the release of a separate strain of MYXV in France and its subsequent spread throughout Europe. The selection of attenuated strains of virus and resistant rabbits mirrored the experience in Australia in a very different environment, albeit with somewhat different rates. Genome sequencing of the progenitor virus and the early radiation, as well as those from the 1990s in Australia and Europe, has shown that although MYXV evolved at high rates there was no conserved route to attenuation or back to virulence. In contrast, it seems that these relatively large viral genomes have the flexibility for multiple pathways that converge on a similar phenotype. Full article
(This article belongs to the Special Issue Poxvirus Evolution)
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Open AccessReview
Poxviral Ankyrin Proteins
Viruses 2015, 7(2), 709-738; https://doi.org/10.3390/v7020709 - 16 Feb 2015
Cited by 18
Abstract
Multiple repeats of the ankyrin motif (ANK) are ubiquitous throughout the kingdoms of life but are absent from most viruses. The main exception to this is the poxvirus family, and specifically the chordopoxviruses, with ANK repeat proteins present in all but three species [...] Read more.
Multiple repeats of the ankyrin motif (ANK) are ubiquitous throughout the kingdoms of life but are absent from most viruses. The main exception to this is the poxvirus family, and specifically the chordopoxviruses, with ANK repeat proteins present in all but three species from separate genera. The poxviral ANK repeat proteins belong to distinct orthologue groups spread over different species, and align well with the phylogeny of their genera. This distribution throughout the chordopoxviruses indicates these proteins were present in an ancestral vertebrate poxvirus, and have since undergone numerous duplication events. Most poxviral ANK repeat proteins contain an unusual topology of multiple ANK motifs starting at the N-terminus with a C-terminal poxviral homologue of the cellular F-box enabling interaction with the cellular SCF ubiquitin ligase complex. The subtle variations between ANK repeat proteins of individual poxviruses suggest an array of different substrates may be bound by these protein-protein interaction domains and, via the F-box, potentially directed to cellular ubiquitination pathways and possible degradation. Known interaction partners of several of these proteins indicate that the NF-κB coordinated anti-viral response is a key target, whilst some poxviral ANK repeat domains also have an F-box independent affect on viral host-range. Full article
(This article belongs to the Special Issue Poxvirus Evolution)
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