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Viral Recombination: Ecology, Evolution and Pathogenesis

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A special issue of Viruses (ISSN 1999-4915).

Deadline for manuscript submissions: closed (28 February 2018) | Viewed by 56999

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Special Issue Editor

Dr. Ken Stedman

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Guest Editor

Center for Life in Extreme Environments, Department of Biology, Portland State University, Room 466, SRTC, 1719 SW 10th Avenue - P.O. Box 751, Portland, OR 97207-0751, USA
Interests: archaeal viruses; archaeal genetics; archaeal evolution; viral recombination; silica coating; vaccine stabilization; virus evolution; viral genomics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Daer Colleagues,

Viral recombination is a central aspect of virus ecology, evolution and pathogenesis. It is even essential for replication of some viruses. Recombination between closely related viruses can generate multiple antigenic variants or even modify host ranges. Recombination between otherwise unrelated viruses generates novel viruses with potentially radically different characteristics and pathogenesis. Recently, it has become clear that viral recombination is much more widespread than previously thought and may occur between DNA and RNA viruses. Nonetheless, the extent and roles of viral recombination are still not completely understood.

This special issue of Viruses is dedicated to explore and discuss aspects of viral recombination. We hope to assemble a collection of research papers and reviews that together will offer a comprehensive view on this rapidly developing field, which reflects our current understanding, and looks toward the future. Topics may include recombination mechanisms, evolutionary aspects of recombination, gene acquisition, emergence of novel viruses, recombination in the development of antigenic variation, and viral replication.

Dr. Ken Stedman
Guest Editor

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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.

Published Papers (11 papers)

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Editorial

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2 pages, 162 KiB

Open AccessEditorial

Viral Recombination: Ecology, Evolution, and Pathogenesis

by Kenneth M. Stedman

Viruses 2018, 10(7), 358; https://0-doi-org.brum.beds.ac.uk/10.3390/v10070358 - 06 Jul 2018

Cited by 7 | Viewed by 2718

Abstract

Recombination between and within virus genomes is being increasingly recognized as a major
driver of virus evolution. Full article

(This article belongs to the Special Issue Viral Recombination: Ecology, Evolution and Pathogenesis)

Research

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14 pages, 12568 KiB

Open AccessArticle

Within-Host Recombination in the Foot-and-Mouth Disease Virus Genome

by Luca Ferretti, Antonello Di Nardo, Benjamin Singer, Lidia Lasecka-Dykes, Grace Logan, Caroline F. Wright, Eva Pérez-Martín, Donald P. King, Tobias J. Tuthill and Paolo Ribeca

Viruses 2018, 10(5), 221; https://0-doi-org.brum.beds.ac.uk/10.3390/v10050221 - 25 Apr 2018

Cited by 20 | Viewed by 6166

Abstract

Recombination is one of the determinants of genetic diversity in the foot-and-mouth disease virus (FMDV). FMDV sequences have a mosaic structure caused by extensive intra- and inter-serotype recombination, with the exception of the capsid-encoding region. While these genome-wide patterns of broad-scale recombination are well studied, not much is known about the patterns of recombination that may exist within infected hosts. In addition, detection of recombination among viruses evolving at the within-host level is challenging due to the similarity of the sequences and the limitations in differentiating recombination from point mutations. Here, we present the first analysis of recombination events between closely related FMDV sequences occurring within buffalo hosts. The detection of these events was made possible by the occurrence of co-infection of two viral swarms with about 1% nucleotide divergence. We found more than 15 recombination events, unequally distributed across eight samples from different animals. The distribution of these events along the FMDV genome was neither uniform nor related to the phylogenetic distribution of recombination breakpoints, suggesting a mismatch between within-host evolutionary pressures and long-term selection for infectivity and transmissibility. Full article

(This article belongs to the Special Issue Viral Recombination: Ecology, Evolution and Pathogenesis)

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16 pages, 5972 KiB

Open AccessArticle

A New Approach to Assessing HSV-1 Recombination during Intercellular Spread

by Gabrielle A. Law, Alix E. Herr, James P. Cwick and Matthew P. Taylor

Viruses 2018, 10(5), 220; https://0-doi-org.brum.beds.ac.uk/10.3390/v10050220 - 25 Apr 2018

Cited by 7 | Viewed by 4434

Abstract

The neuroinvasive Herpes simplex virus type 1 (HSV-1) utilizes intergenomic recombination in order to diversify viral populations. Research efforts to assess HSV-1 recombination are often complicated by the use of attenuating mutations, which differentiate viral progeny but unduly influence the replication and spread. In this work, we generated viruses with markers that allowed for classification of viral progeny with limited attenuation of viral replication. We isolated viruses, harboring either a cyan (C) or yellow (Y) fluorescent protein (FP) expression cassette inserted in two different locations within the viral genome, in order to visually quantify the recombinant progeny based on plaque fluorescence. We found that the FP marked genomes had a limited negative affect on the viral replication and production of progeny virions. A co-infection of the two viruses resulted in recombinant progeny that was dependent on the multiplicity of infection and independent of the time post infection, at a rate that was similar to previous reports. The sequential passage of mixed viral populations revealed a limited change in the distribution of the parental and recombinant progeny. Interestingly, the neuroinvasive spread within neuronal cultures and an in vivo mouse model, revealed large, random shifts in the parental and recombinant distributions in viral populations. In conclusion, our approach highlights the utility of FP expressing viruses in order to provide new insights into mechanisms of HSV-1 recombination. Full article

(This article belongs to the Special Issue Viral Recombination: Ecology, Evolution and Pathogenesis)

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16 pages, 33660 KiB

Open AccessArticle

Full Genome Sequencing Reveals New Southern African Territories Genotypes Bringing Us Closer to Understanding True Variability of Foot-and-Mouth Disease Virus in Africa

by Lidia Lasecka-Dykes, Caroline F. Wright, Antonello Di Nardo, Grace Logan, Valerie Mioulet, Terry Jackson, Tobias J. Tuthill, Nick J. Knowles and Donald P. King

Viruses 2018, 10(4), 192; https://0-doi-org.brum.beds.ac.uk/10.3390/v10040192 - 13 Apr 2018

Cited by 17 | Viewed by 6646

Abstract

Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hooved animals that poses a constant burden on farmers in endemic regions and threatens the livestock industries in disease-free countries. Despite the increased number of publicly available whole genome sequences, FMDV data are biased by the opportunistic nature of sampling. Since whole genomic sequences of Southern African Territories (SAT) are particularly underrepresented, this study sequenced 34 isolates from eastern and southern Africa. Phylogenetic analyses revealed two novel genotypes (that comprised 8/34 of these SAT isolates) which contained unusual 5′ untranslated and non-structural encoding regions. While recombination has occurred between these sequences, phylogeny violation analyses indicated that the high degree of sequence diversity for the novel SAT genotypes has not solely arisen from recombination events. Based on estimates of the timing of ancestral divergence, these data are interpreted as being representative of un-sampled FMDV isolates that have been subjected to geographical isolation within Africa by the effects of the Great African Rinderpest Pandemic (1887–1897), which caused a mass die-out of FMDV-susceptible hosts. These findings demonstrate that further sequencing of African FMDV isolates is likely to reveal more unusual genotypes and will allow for better understanding of natural variability and evolution of FMDV. Full article

(This article belongs to the Special Issue Viral Recombination: Ecology, Evolution and Pathogenesis)

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Graphical abstract

11 pages, 4752 KiB

Open AccessArticle

Pervasive Chimerism in the Replication-Associated Proteins of Uncultured Single-Stranded DNA Viruses

by Darius Kazlauskas, Arvind Varsani and Mart Krupovic

Viruses 2018, 10(4), 187; https://0-doi-org.brum.beds.ac.uk/10.3390/v10040187 - 10 Apr 2018

Cited by 63 | Viewed by 6201

Abstract

Numerous metagenomic studies have uncovered a remarkable diversity of circular replication-associated protein (Rep)-encoding single-stranded (CRESS) DNA viruses, the majority of which are uncultured and unclassified. Unlike capsid proteins, the Reps show significant similarity across different groups of CRESS DNA viruses and have conserved domain organization with the N-terminal nuclease and the C-terminal helicase domain. Consequently, Rep is widely used as a marker for identification, classification and assessment of the diversity of CRESS DNA viruses. However, it has been shown that in certain viruses the Rep nuclease and helicase domains display incongruent evolutionary histories. Here, we systematically evaluated the co-evolutionary patterns of the two Rep domains across classified and unclassified CRESS DNA viruses. Our analysis indicates that the Reps encoded by members of the families Bacilladnaviridae, Circoviridae, Geminiviridae, Genomoviridae, Nanoviridae and Smacoviridae display largely congruent evolutionary patterns in the two domains. By contrast, among the unclassified CRESS DNA viruses, 71% appear to have chimeric Reps. Such massive chimerism suggests that unclassified CRESS DNA viruses represent a dynamic population in which exchange of gene fragments encoding the nuclease and helicase domains is extremely common. Furthermore, purging of the chimeric sequences uncovered six monophyletic Rep groups that may represent new families of CRESS DNA viruses. Full article

(This article belongs to the Special Issue Viral Recombination: Ecology, Evolution and Pathogenesis)

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Graphical abstract

12 pages, 24621 KiB

Open AccessArticle

Passion Fruit Chlorotic Mottle Virus: Molecular Characterization of a New Divergent Geminivirus in Brazil

by Rafaela S. Fontenele, Rayane A. Abreu, Natalia S. Lamas, Dione M. T. Alves-Freitas, Andreza H. Vidal, Raul R. Poppiel, Fernando L. Melo, Cristiano Lacorte, Darren P. Martin, Magnolia A. Campos, Arvind Varsani and Simone G. Ribeiro

Viruses 2018, 10(4), 169; https://0-doi-org.brum.beds.ac.uk/10.3390/v10040169 - 02 Apr 2018

Cited by 42 | Viewed by 6475

Abstract

Brazil is one of the major passion fruit producers worldwide. Viral diseases are among the most important constraints for passion fruit production. Here we identify and characterize a new passion fruit infecting-virus belonging to the family Geminiviridae: passion fruit chlorotic mottle virus (PCMoV). PCMoV is a divergent geminivirus unlike previously characterized passion fruit-infecting geminiviruses that belonged to the genus Begomovirus. Among the presently known geminiviruses, it is most closely related to, and shares ~62% genome-wide identity with citrus chlorotic dwarf associated virus (CCDaV) and camelia chlorotic dwarf associated virus (CaCDaV). The 3743 nt PCMoV genome encodes a capsid protein (CP) and replication-associated protein (Rep) that respectively share 56 and 60% amino acid identity with those encoded by CaCDaV. The CPs of PCMoV, CCDaV, and CaCDaV cluster with those of begomovirus whereas their Reps with those of becurtoviruses. Hence, these viruses likely represent a lineage of recombinant begomo-like and becurto-like ancestral viruses. Furthermore, PCMoV, CCDaV, and CaCDaV genomes are ~12–30% larger than monopartite geminiviruses and this is primarily due to the encoded movement protein (MP; 891–921 nt) and this MP is most closely related to that encoded by the DNA-B component of bipartite begomoviruses. Hence, PCMoV, CCDaV, and CaCDaV lineage of viruses may represent molecules in an intermediary step in the evolution of bipartite begomoviruses (~5.3 kb) from monopartite geminiviruses (~2.7–3 kb). An infectious clone of PCMoV systemically infected Nicotiana benthamina, Arabidopsis thaliana, and Passiflora edulis. Full article

(This article belongs to the Special Issue Viral Recombination: Ecology, Evolution and Pathogenesis)

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22 pages, 3959 KiB

Open AccessArticle

Intermolecular RNA Recombination Occurs at Different Frequencies in Alternate Forms of Brome Mosaic Virus RNA Replication Compartments

by Hernan Garcia-Ruiz, Arturo Diaz and Paul Ahlquist

Viruses 2018, 10(3), 131; https://0-doi-org.brum.beds.ac.uk/10.3390/v10030131 - 15 Mar 2018

Cited by 15 | Viewed by 4168

Abstract

Positive-strand RNA viruses replicate their genomes in membrane-bound replication compartments. Brome mosaic virus (BMV) replicates in vesicular invaginations of the endoplasmic reticulum membrane. BMV has served as a productive model system to study processes like virus-host interactions, RNA replication and recombination. Here we present multiple lines of evidence showing that the structure of the viral RNA replication compartments plays a fundamental role and that recruitment of parental RNAs to a common replication compartment is a limiting step in intermolecular RNA recombination. We show that a previously defined requirement for an RNA recruitment element on both parental RNAs is not to function as a preferred crossover site, but in order for individual RNAs to be recruited into the replication compartments. Moreover, modulating the form of the replication compartments from spherular vesicles (spherules) to more expansive membrane layers increased intermolecular RNA recombination frequency by 200- to 1000-fold. We propose that intermolecular RNA recombination requires parental RNAs to be recruited into replication compartments as monomers, and that recruitment of multiple RNAs into a contiguous space is much more common for layers than for spherules. These results could explain differences in recombination frequencies between viruses that replicate in association with smaller spherules versus larger double-membrane vesicles and convoluted membranes. Full article

(This article belongs to the Special Issue Viral Recombination: Ecology, Evolution and Pathogenesis)

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13 pages, 1640 KiB

Open AccessArticle

Recombinant Goose Circoviruses Circulating in Domesticated and Wild Geese in Poland

by Tomasz Stenzel, Daria Dziewulska, Brejnev M. Muhire, Penelope Hartnady, Simona Kraberger, Darren P. Martin and Arvind Varsani

Viruses 2018, 10(3), 107; https://doi.org/10.3390/v10030107 - 02 Mar 2018

Cited by 14 | Viewed by 4042

Abstract

Circoviruses are circular single-stranded DNA (ssDNA) viruses that infect a variety of animals, both domestic and wild. Circovirus infection in birds is associated with immunosuppression and this in turn predisposes the infected animals to secondary infections that can lead to mortality. Farmed geese (Anser anser) in many parts of the world are infected with circoviruses. The majority of the current genomic information for goose circoviruses (GoCVs) (n = 40) are from birds sampled in China and Taiwan, and only two genome sequences are available from Europe (Germany and Poland). In this study, we sampled 23 wild and 19 domestic geese from the Gopło Lake area in Poland. We determined the genomes of GoCV from 21 geese; 14 domestic Greylag geese (Anser anser), three wild Greylag geese (A. anser), three bean geese (A. fabalis), and one white fronted goose (A. albifrons). These genomes share 83–95% nucleotide pairwise identities with previously identified GoCV genomes, most are recombinants with exchanged fragment sizes up to 50% of the genome. Higher diversity levels can be seen within the genomes from domestic geese compared with those from wild geese. In the GoCV capsid protein (cp) and replication associated protein (rep) gene sequences we found that episodic positive selection appears to largely mirror those of beak and feather disease virus and pigeon circovirus. Analysis of the secondary structure of the ssDNA genome revealed a conserved stem-loop structure with the G-C rich stem having a high degree of negative selection on these nucleotides. Full article

(This article belongs to the Special Issue Viral Recombination: Ecology, Evolution and Pathogenesis)

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1665 KiB

Open AccessArticle

Distribution and Inferred Evolutionary Characteristics of a Chimeric ssDNA Virus Associated with Intertidal Marine Isopods

by Kalia S. I. Bistolas, Ryan M. Besemer, Lars G. Rudstam and Ian Hewson

Viruses 2017, 9(12), 361; https://0-doi-org.brum.beds.ac.uk/10.3390/v9120361 - 26 Nov 2017

Cited by 8 | Viewed by 5044

Abstract

Aquatic invertebrates are common reservoirs of a rapidly expanding group of circular Rep-encoding ssDNA (CRESS-DNA) viruses. This study identified and explored the phylogenetic relationship between novel CRESS-DNA viral genotypes associated with Pacific intertidal isopods Idotea wosnesenskii, Idotea resecata, and Gnorimosphaeroma oregonensis. One genotype associated with I. wosnesenskii, IWaV278, shared sequence similarity and genomic features with Tombusviridae (ssRNA) and Circoviridae (ssDNA) genomes and was putatively assigned to the Cruciviridae clade comprising chimeric viruses. The complete genome of IWaV278 (3478 nt) was computationally completed, validated via Sanger sequencing, and exhibited sequence conservation and codon usage patterns analogous to other members of the Cruciviridae. Viral surveillance (qPCR) indicated that this virus was temporally transient (present in 2015, but not 2017), specific to I. wosnesenskii at a single collection site (Washington, DC, USA), more prevalent among male specimens, and frequently detected within exoskeletal structures. 18S rRNA sequences identified two alveolate protists associated with IWaV278-positive tissues and mechanical epibiont removal of ciliated exoskeletal structures eliminated viral detection, suggesting that the putative host of IWaV278 may be an epibiont of I. wosnesenskii. This investigation provides additional phylogenetic evidence to resolve Cruciviridae evolution and offers insight into the biogeography, specificity, and potential host of a crucivirus genotype. Full article

(This article belongs to the Special Issue Viral Recombination: Ecology, Evolution and Pathogenesis)

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2787 KiB

Open AccessArticle

Pressure for Pattern-Specific Intertypic Recombination between Sabin Polioviruses: Evolutionary Implications

by Ekaterina Korotkova, Majid Laassri, Tatiana Zagorodnyaya, Svetlana Petrovskaya, Elvira Rodionova, Elena Cherkasova, Anatoly Gmyl, Olga E. Ivanova, Tatyana P. Eremeeva, Galina Y. Lipskaya, Vadim I. Agol and Konstantin Chumakov

Viruses 2017, 9(11), 353; https://0-doi-org.brum.beds.ac.uk/10.3390/v9110353 - 22 Nov 2017

Cited by 19 | Viewed by 4425

Abstract

Complete genomic sequences of a non-redundant set of 70 recombinants between three serotypes of attenuated Sabin polioviruses as well as location (based on partial sequencing) of crossover sites of 28 additional recombinants were determined and compared with the previously published data. It is demonstrated that the genomes of Sabin viruses contain distinct strain-specific segments that are eliminated by recombination. The presumed low fitness of these segments could be linked to mutations acquired upon derivation of the vaccine strains and/or may have been present in wild-type parents of Sabin viruses. These “weak” segments contribute to the propensity of these viruses to recombine with each other and with other enteroviruses as well as determine the choice of crossover sites. The knowledge of location of such segments opens additional possibilities for the design of more genetically stable and/or more attenuated variants, i.e., candidates for new oral polio vaccines. The results also suggest that the genome of wild polioviruses, and, by generalization, of other RNA viruses, may harbor hidden low-fitness segments that can be readily eliminated only by recombination. Full article

(This article belongs to the Special Issue Viral Recombination: Ecology, Evolution and Pathogenesis)

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Review

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21 pages, 11936 KiB

Open AccessReview

Changes in the EV-A71 Genome through Recombination and Spontaneous Mutations: Impact on Virulence

by Madiiha Bibi Mandary and Chit Laa Poh

Viruses 2018, 10(6), 320; https://0-doi-org.brum.beds.ac.uk/10.3390/v10060320 - 12 Jun 2018

Cited by 22 | Viewed by 5585

Abstract

Enterovirus 71 (EV-A71) is a major etiological agent of hand, foot and mouth disease (HFMD) that mainly affects young children less than five years old. The onset of severe HFMD is due to neurological complications bringing about acute flaccid paralysis and pulmonary oedema. In this review, we address how genetic events such as recombination and spontaneous mutations could change the genomic organization of EV-A71, leading to an impact on viral virulence. An understanding of the recombination mechanism of the poliovirus and non-polio enteroviruses will provide further evidence of the emergence of novel strains responsible for fatal HFMD outbreaks. We aim to see if the virulence of EV-A71 is contributed solely by the presence of fatal strains or is due to the co-operation of quasispecies within a viral population. The phenomenon of quasispecies within the poliovirus is discussed to reflect viral fitness, virulence and its implications for EV-A71. Ultimately, this review gives an insight into the evolution patterns of EV-A71 by looking into its recombination history and how spontaneous mutations would affect its virulence. Full article

(This article belongs to the Special Issue Viral Recombination: Ecology, Evolution and Pathogenesis)

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