Phylogenomic analysis of two co-circulating canine distemper virus lineages in Colombia
Canine distemper virus (CDV) is considered a reemerging disease-causing agent in domestic dogs because it presents high divergence among circulating strains worldwide. In Colombia, the South America-3 and South America/North America-4 lineages co-circulate in domestic dogs, both in the Medellin metr...
- Autores:
-
Duque Valencia, July
Diaz, Francisco Javier
Ruiz Sáenz, Julián
- Tipo de recurso:
- Article of investigation
- Fecha de publicación:
- 2020
- Institución:
- Universidad Cooperativa de Colombia
- Repositorio:
- Repositorio UCC
- Idioma:
- OAI Identifier:
- oai:repository.ucc.edu.co:20.500.12494/32937
- Acceso en línea:
- https://hdl.handle.net/20.500.12494/32937
- Palabra clave:
- Phylogenomics
Reemerging
Lineages co-circulation
Genome
CDV
- Rights
- openAccess
- License
- Atribución – No comercial – Compartir igual
id |
COOPER2_97896ca68bd9b2e740b009e3bec84695 |
---|---|
oai_identifier_str |
oai:repository.ucc.edu.co:20.500.12494/32937 |
network_acronym_str |
COOPER2 |
network_name_str |
Repositorio UCC |
repository_id_str |
|
dc.title.spa.fl_str_mv |
Phylogenomic analysis of two co-circulating canine distemper virus lineages in Colombia |
title |
Phylogenomic analysis of two co-circulating canine distemper virus lineages in Colombia |
spellingShingle |
Phylogenomic analysis of two co-circulating canine distemper virus lineages in Colombia Phylogenomics Reemerging Lineages co-circulation Genome CDV |
title_short |
Phylogenomic analysis of two co-circulating canine distemper virus lineages in Colombia |
title_full |
Phylogenomic analysis of two co-circulating canine distemper virus lineages in Colombia |
title_fullStr |
Phylogenomic analysis of two co-circulating canine distemper virus lineages in Colombia |
title_full_unstemmed |
Phylogenomic analysis of two co-circulating canine distemper virus lineages in Colombia |
title_sort |
Phylogenomic analysis of two co-circulating canine distemper virus lineages in Colombia |
dc.creator.fl_str_mv |
Duque Valencia, July Diaz, Francisco Javier Ruiz Sáenz, Julián |
dc.contributor.author.none.fl_str_mv |
Duque Valencia, July Diaz, Francisco Javier Ruiz Sáenz, Julián |
dc.subject.spa.fl_str_mv |
Phylogenomics Reemerging Lineages co-circulation Genome CDV |
topic |
Phylogenomics Reemerging Lineages co-circulation Genome CDV |
description |
Canine distemper virus (CDV) is considered a reemerging disease-causing agent in domestic dogs because it presents high divergence among circulating strains worldwide. In Colombia, the South America-3 and South America/North America-4 lineages co-circulate in domestic dogs, both in the Medellin metropolitan area. In this paper, two full CDV genomes from each viral lineage circulating in Medellin were sequenced; we explored the phylogenetic relationship with the available genome sequences; we described the presence of CDV mutations in the South America-3 and South America/North America-4 lineages associated with adaptation to human cells and a crossing of the species barrier and pathogenicity; and we established the evolutionary rates and time of the closest common ancestor for each gene and characterized the presentation of multiple genomic sites by positive selection |
publishDate |
2020 |
dc.date.issued.none.fl_str_mv |
2020-01-01 |
dc.date.accessioned.none.fl_str_mv |
2021-01-28T17:14:44Z |
dc.date.available.none.fl_str_mv |
2021-01-28T17:14:44Z |
dc.type.none.fl_str_mv |
Artículos Científicos |
dc.type.coar.none.fl_str_mv |
http://purl.org/coar/resource_type/c_2df8fbb1 |
dc.type.coarversion.none.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
dc.type.driver.none.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.version.none.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
http://purl.org/coar/resource_type/c_2df8fbb1 |
status_str |
publishedVersion |
dc.identifier.issn.spa.fl_str_mv |
2076-0817 |
dc.identifier.uri.spa.fl_str_mv |
doi.org/10.3390/pathogens9010026 |
dc.identifier.uri.none.fl_str_mv |
https://hdl.handle.net/20.500.12494/32937 |
dc.identifier.bibliographicCitation.spa.fl_str_mv |
Duque-Valencia J, Diaz FJ, Ruiz-Saenz J. Phylogenomic Analysis of Two Co-Circulating Canine Distemper Virus Lineages in Colombia. Pathogens. 2020; 9(1):26. https://doi.org/10.3390/pathogens9010026 |
identifier_str_mv |
2076-0817 doi.org/10.3390/pathogens9010026 Duque-Valencia J, Diaz FJ, Ruiz-Saenz J. Phylogenomic Analysis of Two Co-Circulating Canine Distemper Virus Lineages in Colombia. Pathogens. 2020; 9(1):26. https://doi.org/10.3390/pathogens9010026 |
url |
https://hdl.handle.net/20.500.12494/32937 |
dc.relation.isversionof.spa.fl_str_mv |
https://www.mdpi.com/2076-0817/9/1/26 |
dc.relation.ispartofjournal.spa.fl_str_mv |
Pathogens |
dc.relation.references.spa.fl_str_mv |
MacLachlan, N.; Dubovi, E.; Fenner, F. Fenner’s Veterinary Virology, 4th ed.; Academic Press: Boston, MA, USA, 2011; pp. 299–325. Martinez-Gutierrez, M.; Ruiz-Saenz, J. Diversity of susceptible hosts in canine distemper virus infection: A systematic review and data synthesis. BMC Vet. Res. 2016, 12, 78 International Committee on Taxonomy of Viruses. International Committee on Taxonomy of Viruses (ICTV). 2019. Available online: https://talk.ictvonline.org/taxonomy/ (accessed on 10 December 2019). Lunardi, M.; Darold, G.M.; Amude, A.M.; Headley, S.A.; Sonne, L.; Yamauchi, K.C.I.; Boabaid, F.M.; Alfieri, A.F.; Alfieri, A.A. Canine distemper virus active infection in order pilosa, family myrmecophagidae, species tamandua tetradactyla. Vet. Microbiol. 2018, 220, 7–11 Chinnakannan, S.K.; Nanda, S.K.; Baron, M.D. Morbillivirus v proteins exhibit multiple mechanisms to block type 1 and type 2 interferon signalling pathways. PLoS ONE 2013, 8, e57063 Schuhmann, K.M.; Pfaller, C.K.; Conzelmann, K.K. The measles virus v protein binds to p65 (rela) to suppress nf-kappab activity. J. Virol. 2011, 85, 3162–3171 Duque-Valencia, J.; Sarute, N.; Olarte-Castillo, X.A.; Ruiz-Saenz, J. Evolution and interspecies transmission of canine distemper virus-an outlook of the diverse evolutionary landscapes of a multi-host virus. Viruses 2019, 11, 582. Martella, V.; Bianchi, A.; Bertoletti, I.; Pedrotti, L.; Gugiatti, A.; Catella, A.; Cordioli, P.; Lucente, M.S.; Elia, G.; Buonavoglia, C. Canine distemper epizootic among red foxes, Italy, 2009. Emerg. Infect. Dis. 2010, 16, 2007. Espinal, M.A.; Diaz, F.J.; Ruiz-Saenz, J. Phylogenetic evidence of a new canine distemper virus lineage among domestic dogs in Colombia, South America. Vet. Microbiol. 2014, 172, 168–176. Pope, J.P.; Miller, D.L.; Riley, M.C.; Anis, E.; Wilkes, R.P. Characterization of a novel canine distemper virus causing disease in wildlife. J. Vet. Diagn. Investig. 2016, 28, 506–513 |
dc.rights.license.none.fl_str_mv |
Atribución – No comercial – Compartir igual |
dc.rights.accessrights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
dc.rights.coar.none.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
rights_invalid_str_mv |
Atribución – No comercial – Compartir igual http://purl.org/coar/access_right/c_abf2 |
eu_rights_str_mv |
openAccess |
dc.format.extent.spa.fl_str_mv |
26 |
dc.coverage.temporal.spa.fl_str_mv |
9 (1) |
dc.publisher.spa.fl_str_mv |
MDPI Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Medicina Veterinaría y Zootecnia, Bucaramanga |
dc.publisher.program.spa.fl_str_mv |
Medicina veterinaria y zootecnia |
dc.publisher.place.spa.fl_str_mv |
Bucaramanga |
institution |
Universidad Cooperativa de Colombia |
bitstream.url.fl_str_mv |
https://repository.ucc.edu.co/bitstreams/fe65ff3f-3d80-4dfd-b090-f81845e0fa90/download https://repository.ucc.edu.co/bitstreams/03a26ba1-4290-48df-b0a8-54302e143e75/download https://repository.ucc.edu.co/bitstreams/371e94f9-239b-4796-a1cc-9e13b6101ea0/download https://repository.ucc.edu.co/bitstreams/235bf755-edc4-451f-9776-41ab3acf8ca8/download https://repository.ucc.edu.co/bitstreams/6d25db6a-ec8f-4a90-9294-f3943d8dda2c/download https://repository.ucc.edu.co/bitstreams/7412e19c-b7c4-4b9c-a58b-a4aae2bb2953/download https://repository.ucc.edu.co/bitstreams/ef627960-121d-429e-987c-3ddc844fd752/download |
bitstream.checksum.fl_str_mv |
3bce4f7ab09dfc588f126e1e36e98a45 d5d60900f34a8197921c42a250bc672c 5623b640b1e5839aa9ccd942424f8af9 f8597c8e455db18edd4b60c80b916ec2 8296861c64c449af79651deaab13b998 07b1004c122d62ad638eea7eecc604b5 7b27bbbcc7baa75b901a48c6a8777bd5 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositorio Institucional Universidad Cooperativa de Colombia |
repository.mail.fl_str_mv |
bdigital@metabiblioteca.com |
_version_ |
1811565165755236352 |
spelling |
Duque Valencia, JulyDiaz, Francisco JavierRuiz Sáenz, Julián9 (1)2021-01-28T17:14:44Z2021-01-28T17:14:44Z2020-01-012076-0817doi.org/10.3390/pathogens9010026https://hdl.handle.net/20.500.12494/32937Duque-Valencia J, Diaz FJ, Ruiz-Saenz J. Phylogenomic Analysis of Two Co-Circulating Canine Distemper Virus Lineages in Colombia. Pathogens. 2020; 9(1):26. https://doi.org/10.3390/pathogens9010026Canine distemper virus (CDV) is considered a reemerging disease-causing agent in domestic dogs because it presents high divergence among circulating strains worldwide. In Colombia, the South America-3 and South America/North America-4 lineages co-circulate in domestic dogs, both in the Medellin metropolitan area. In this paper, two full CDV genomes from each viral lineage circulating in Medellin were sequenced; we explored the phylogenetic relationship with the available genome sequences; we described the presence of CDV mutations in the South America-3 and South America/North America-4 lineages associated with adaptation to human cells and a crossing of the species barrier and pathogenicity; and we established the evolutionary rates and time of the closest common ancestor for each gene and characterized the presentation of multiple genomic sites by positive selectionhttp://scienti.colciencias.gov.co:8081/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0000153095https://orcid.org/0000-0002-1447-1458https://scienti.minciencias.gov.co/gruplac/jsp/visualiza/visualizagr.jsp?nro=00000000000695julian.ruizs@campusucc.edu.cohttps://scholar.google.com/citations?user=o3Y7mZwAAAAJ&hl=es26MDPIUniversidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Medicina Veterinaría y Zootecnia, BucaramangaMedicina veterinaria y zootecniaBucaramangahttps://www.mdpi.com/2076-0817/9/1/26PathogensMacLachlan, N.; Dubovi, E.; Fenner, F. Fenner’s Veterinary Virology, 4th ed.; Academic Press: Boston, MA, USA, 2011; pp. 299–325.Martinez-Gutierrez, M.; Ruiz-Saenz, J. Diversity of susceptible hosts in canine distemper virus infection: A systematic review and data synthesis. BMC Vet. Res. 2016, 12, 78International Committee on Taxonomy of Viruses. International Committee on Taxonomy of Viruses (ICTV). 2019. Available online: https://talk.ictvonline.org/taxonomy/ (accessed on 10 December 2019).Lunardi, M.; Darold, G.M.; Amude, A.M.; Headley, S.A.; Sonne, L.; Yamauchi, K.C.I.; Boabaid, F.M.; Alfieri, A.F.; Alfieri, A.A. Canine distemper virus active infection in order pilosa, family myrmecophagidae, species tamandua tetradactyla. Vet. Microbiol. 2018, 220, 7–11Chinnakannan, S.K.; Nanda, S.K.; Baron, M.D. Morbillivirus v proteins exhibit multiple mechanisms to block type 1 and type 2 interferon signalling pathways. PLoS ONE 2013, 8, e57063Schuhmann, K.M.; Pfaller, C.K.; Conzelmann, K.K. The measles virus v protein binds to p65 (rela) to suppress nf-kappab activity. J. Virol. 2011, 85, 3162–3171Duque-Valencia, J.; Sarute, N.; Olarte-Castillo, X.A.; Ruiz-Saenz, J. Evolution and interspecies transmission of canine distemper virus-an outlook of the diverse evolutionary landscapes of a multi-host virus. Viruses 2019, 11, 582.Martella, V.; Bianchi, A.; Bertoletti, I.; Pedrotti, L.; Gugiatti, A.; Catella, A.; Cordioli, P.; Lucente, M.S.; Elia, G.; Buonavoglia, C. Canine distemper epizootic among red foxes, Italy, 2009. Emerg. Infect. Dis. 2010, 16, 2007.Espinal, M.A.; Diaz, F.J.; Ruiz-Saenz, J. Phylogenetic evidence of a new canine distemper virus lineage among domestic dogs in Colombia, South America. Vet. Microbiol. 2014, 172, 168–176.Pope, J.P.; Miller, D.L.; Riley, M.C.; Anis, E.; Wilkes, R.P. Characterization of a novel canine distemper virus causing disease in wildlife. J. Vet. Diagn. Investig. 2016, 28, 506–513PhylogenomicsReemergingLineages co-circulationGenomeCDVPhylogenomic analysis of two co-circulating canine distemper virus lineages in ColombiaArtículos Científicoshttp://purl.org/coar/resource_type/c_2df8fbb1http://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionAtribución – No comercial – Compartir igualinfo:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2PublicationLICENSElicense.txtlicense.txttext/plain; charset=utf-84334https://repository.ucc.edu.co/bitstreams/fe65ff3f-3d80-4dfd-b090-f81845e0fa90/download3bce4f7ab09dfc588f126e1e36e98a45MD54ORIGINAL2021_phylogenomic_analysis_two_co-circulating.pdf2021_phylogenomic_analysis_two_co-circulating.pdfapplication/pdf887124https://repository.ucc.edu.co/bitstreams/03a26ba1-4290-48df-b0a8-54302e143e75/downloadd5d60900f34a8197921c42a250bc672cMD512021_phylogenomic_analysis_two_co-circulating-FormatoLicenciaUso.pdf2021_phylogenomic_analysis_two_co-circulating-FormatoLicenciaUso.pdfapplication/pdf207793https://repository.ucc.edu.co/bitstreams/371e94f9-239b-4796-a1cc-9e13b6101ea0/download5623b640b1e5839aa9ccd942424f8af9MD53THUMBNAIL2021_phylogenomic_analysis_two_co-circulating.pdf.jpg2021_phylogenomic_analysis_two_co-circulating.pdf.jpgGenerated Thumbnailimage/jpeg5365https://repository.ucc.edu.co/bitstreams/235bf755-edc4-451f-9776-41ab3acf8ca8/downloadf8597c8e455db18edd4b60c80b916ec2MD552021_phylogenomic_analysis_two_co-circulating-FormatoLicenciaUso.pdf.jpg2021_phylogenomic_analysis_two_co-circulating-FormatoLicenciaUso.pdf.jpgGenerated Thumbnailimage/jpeg5448https://repository.ucc.edu.co/bitstreams/6d25db6a-ec8f-4a90-9294-f3943d8dda2c/download8296861c64c449af79651deaab13b998MD56TEXT2021_phylogenomic_analysis_two_co-circulating.pdf.txt2021_phylogenomic_analysis_two_co-circulating.pdf.txtExtracted texttext/plain49310https://repository.ucc.edu.co/bitstreams/7412e19c-b7c4-4b9c-a58b-a4aae2bb2953/download07b1004c122d62ad638eea7eecc604b5MD572021_phylogenomic_analysis_two_co-circulating-FormatoLicenciaUso.pdf.txt2021_phylogenomic_analysis_two_co-circulating-FormatoLicenciaUso.pdf.txtExtracted texttext/plain5906https://repository.ucc.edu.co/bitstreams/ef627960-121d-429e-987c-3ddc844fd752/download7b27bbbcc7baa75b901a48c6a8777bd5MD5820.500.12494/32937oai:repository.ucc.edu.co:20.500.12494/329372024-08-09 12:27:28.173open.accesshttps://repository.ucc.edu.coRepositorio Institucional Universidad Cooperativa de Colombiabdigital@metabiblioteca.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 |