Massive depletion of bovine leukemia virus proviral clones located in genomic transcriptionally active sites during primary infection

Autores
Gillet, Nicolas A.; Gutiérrez, Gerónimo; Rodriguez, Sabrina M.; de Brogniez, Alix; Renotte, Nathelie; Alvarez, Irene; Trono, Karina Gabriela; Willems, Luc
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Deltaretroviruses such as human T-lymphotropic virus type 1 (HTLV-1) and bovine leukemia virus (BLV) induce a persistent infection that remains generally asymptomatic but can also lead to leukemia or lymphoma. These viruses replicate by infecting new lymphocytes (i.e. the infectious cycle) or via clonal expansion of the infected cells (mitotic cycle). The relative importance of these two cycles in viral replication varies during infection. The majority of infected clones are created early before the onset of an efficient immune response. Later on, the main replication route is mitotic expansion of pre-existing infected clones. Due to the paucity of available samples and for ethical reasons, only scarce data is available on early infection by HTLV-1. Therefore, we addressed this question in a comparative BLV model. We used high-throughput sequencing to map and quantify the insertion sites of the provirus in order to monitor the clonality of the BLV-infected cells population (i.e. the number of distinct clones and abundance of each clone). We found that BLV propagation shifts from cell neoinfection to clonal proliferation in about 2 months from inoculation. Initially, BLV proviral integration significantly favors transcribed regions of the genome. Negative selection then eliminates 97% of the clones detected at seroconversion and disfavors BLV-infected cells carrying a provirus located close to a promoter or a gene. Nevertheless, among the surviving proviruses, clone abundance positively correlates with proximity of the provirus to a transcribed region. Two opposite forces thus operate during primary infection and dictate the fate of long term clonal composition: (1) initial integration inside genes or promoters and (2) host negative selection disfavoring proviruses located next to transcribed regions. The result of this initial response will contribute to the proviral load set point value as clonal abundance will benefit from carrying a provirus in transcribed regions.
Fil: Gillet, Nicolas A.. Université de Liege; Bélgica
Fil: Gutiérrez, Gerónimo. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rodriguez, Sabrina M.. Université de Liege; Bélgica
Fil: de Brogniez, Alix. Université de Liege; Bélgica
Fil: Renotte, Nathelie. Université de Liege; Bélgica
Fil: Alvarez, Irene. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Trono, Karina Gabriela. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Willems, Luc. Université de Liege; Bélgica
Materia
BLV
REPLICATION
CLONES
INFECTION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/23871
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/23871
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Massive depletion of bovine leukemia virus proviral clones located in genomic transcriptionally active sites during primary infectionGillet, Nicolas A.Gutiérrez, GerónimoRodriguez, Sabrina M.de Brogniez, AlixRenotte, NathelieAlvarez, IreneTrono, Karina GabrielaWillems, LucBLVREPLICATIONCLONESINFECTIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Deltaretroviruses such as human T-lymphotropic virus type 1 (HTLV-1) and bovine leukemia virus (BLV) induce a persistent infection that remains generally asymptomatic but can also lead to leukemia or lymphoma. These viruses replicate by infecting new lymphocytes (i.e. the infectious cycle) or via clonal expansion of the infected cells (mitotic cycle). The relative importance of these two cycles in viral replication varies during infection. The majority of infected clones are created early before the onset of an efficient immune response. Later on, the main replication route is mitotic expansion of pre-existing infected clones. Due to the paucity of available samples and for ethical reasons, only scarce data is available on early infection by HTLV-1. Therefore, we addressed this question in a comparative BLV model. We used high-throughput sequencing to map and quantify the insertion sites of the provirus in order to monitor the clonality of the BLV-infected cells population (i.e. the number of distinct clones and abundance of each clone). We found that BLV propagation shifts from cell neoinfection to clonal proliferation in about 2 months from inoculation. Initially, BLV proviral integration significantly favors transcribed regions of the genome. Negative selection then eliminates 97% of the clones detected at seroconversion and disfavors BLV-infected cells carrying a provirus located close to a promoter or a gene. Nevertheless, among the surviving proviruses, clone abundance positively correlates with proximity of the provirus to a transcribed region. Two opposite forces thus operate during primary infection and dictate the fate of long term clonal composition: (1) initial integration inside genes or promoters and (2) host negative selection disfavoring proviruses located next to transcribed regions. The result of this initial response will contribute to the proviral load set point value as clonal abundance will benefit from carrying a provirus in transcribed regions.Fil: Gillet, Nicolas A.. Université de Liege; BélgicaFil: Gutiérrez, Gerónimo. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rodriguez, Sabrina M.. Université de Liege; BélgicaFil: de Brogniez, Alix. Université de Liege; BélgicaFil: Renotte, Nathelie. Université de Liege; BélgicaFil: Alvarez, Irene. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Trono, Karina Gabriela. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Willems, Luc. Université de Liege; BélgicaPublic Library of Science2013-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/23871Gillet, Nicolas A.; Gutiérrez, Gerónimo; Rodriguez, Sabrina M.; de Brogniez, Alix; Renotte, Nathelie; et al.; Massive depletion of bovine leukemia virus proviral clones located in genomic transcriptionally active sites during primary infection; Public Library of Science; Plos Pathogens; 9; 10; 10-2013; 1-13; e10036871553-7366CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1003687info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.ppat.1003687info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:07:26Zoai:ri.conicet.gov.ar:11336/23871instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:07:27.113CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Massive depletion of bovine leukemia virus proviral clones located in genomic transcriptionally active sites during primary infection
title Massive depletion of bovine leukemia virus proviral clones located in genomic transcriptionally active sites during primary infection
spellingShingle Massive depletion of bovine leukemia virus proviral clones located in genomic transcriptionally active sites during primary infection
Gillet, Nicolas A.
BLV
REPLICATION
CLONES
INFECTION
title_short Massive depletion of bovine leukemia virus proviral clones located in genomic transcriptionally active sites during primary infection
title_full Massive depletion of bovine leukemia virus proviral clones located in genomic transcriptionally active sites during primary infection
title_fullStr Massive depletion of bovine leukemia virus proviral clones located in genomic transcriptionally active sites during primary infection
title_full_unstemmed Massive depletion of bovine leukemia virus proviral clones located in genomic transcriptionally active sites during primary infection
title_sort Massive depletion of bovine leukemia virus proviral clones located in genomic transcriptionally active sites during primary infection
dc.creator.none.fl_str_mv Gillet, Nicolas A.
Gutiérrez, Gerónimo
Rodriguez, Sabrina M.
de Brogniez, Alix
Renotte, Nathelie
Alvarez, Irene
Trono, Karina Gabriela
Willems, Luc
author Gillet, Nicolas A.
author_facet Gillet, Nicolas A.
Gutiérrez, Gerónimo
Rodriguez, Sabrina M.
de Brogniez, Alix
Renotte, Nathelie
Alvarez, Irene
Trono, Karina Gabriela
Willems, Luc
author_role author
author2 Gutiérrez, Gerónimo
Rodriguez, Sabrina M.
de Brogniez, Alix
Renotte, Nathelie
Alvarez, Irene
Trono, Karina Gabriela
Willems, Luc
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BLV
REPLICATION
CLONES
INFECTION
topic BLV
REPLICATION
CLONES
INFECTION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Deltaretroviruses such as human T-lymphotropic virus type 1 (HTLV-1) and bovine leukemia virus (BLV) induce a persistent infection that remains generally asymptomatic but can also lead to leukemia or lymphoma. These viruses replicate by infecting new lymphocytes (i.e. the infectious cycle) or via clonal expansion of the infected cells (mitotic cycle). The relative importance of these two cycles in viral replication varies during infection. The majority of infected clones are created early before the onset of an efficient immune response. Later on, the main replication route is mitotic expansion of pre-existing infected clones. Due to the paucity of available samples and for ethical reasons, only scarce data is available on early infection by HTLV-1. Therefore, we addressed this question in a comparative BLV model. We used high-throughput sequencing to map and quantify the insertion sites of the provirus in order to monitor the clonality of the BLV-infected cells population (i.e. the number of distinct clones and abundance of each clone). We found that BLV propagation shifts from cell neoinfection to clonal proliferation in about 2 months from inoculation. Initially, BLV proviral integration significantly favors transcribed regions of the genome. Negative selection then eliminates 97% of the clones detected at seroconversion and disfavors BLV-infected cells carrying a provirus located close to a promoter or a gene. Nevertheless, among the surviving proviruses, clone abundance positively correlates with proximity of the provirus to a transcribed region. Two opposite forces thus operate during primary infection and dictate the fate of long term clonal composition: (1) initial integration inside genes or promoters and (2) host negative selection disfavoring proviruses located next to transcribed regions. The result of this initial response will contribute to the proviral load set point value as clonal abundance will benefit from carrying a provirus in transcribed regions.
Fil: Gillet, Nicolas A.. Université de Liege; Bélgica
Fil: Gutiérrez, Gerónimo. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rodriguez, Sabrina M.. Université de Liege; Bélgica
Fil: de Brogniez, Alix. Université de Liege; Bélgica
Fil: Renotte, Nathelie. Université de Liege; Bélgica
Fil: Alvarez, Irene. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Trono, Karina Gabriela. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Willems, Luc. Université de Liege; Bélgica
description Deltaretroviruses such as human T-lymphotropic virus type 1 (HTLV-1) and bovine leukemia virus (BLV) induce a persistent infection that remains generally asymptomatic but can also lead to leukemia or lymphoma. These viruses replicate by infecting new lymphocytes (i.e. the infectious cycle) or via clonal expansion of the infected cells (mitotic cycle). The relative importance of these two cycles in viral replication varies during infection. The majority of infected clones are created early before the onset of an efficient immune response. Later on, the main replication route is mitotic expansion of pre-existing infected clones. Due to the paucity of available samples and for ethical reasons, only scarce data is available on early infection by HTLV-1. Therefore, we addressed this question in a comparative BLV model. We used high-throughput sequencing to map and quantify the insertion sites of the provirus in order to monitor the clonality of the BLV-infected cells population (i.e. the number of distinct clones and abundance of each clone). We found that BLV propagation shifts from cell neoinfection to clonal proliferation in about 2 months from inoculation. Initially, BLV proviral integration significantly favors transcribed regions of the genome. Negative selection then eliminates 97% of the clones detected at seroconversion and disfavors BLV-infected cells carrying a provirus located close to a promoter or a gene. Nevertheless, among the surviving proviruses, clone abundance positively correlates with proximity of the provirus to a transcribed region. Two opposite forces thus operate during primary infection and dictate the fate of long term clonal composition: (1) initial integration inside genes or promoters and (2) host negative selection disfavoring proviruses located next to transcribed regions. The result of this initial response will contribute to the proviral load set point value as clonal abundance will benefit from carrying a provirus in transcribed regions.
publishDate 2013
dc.date.none.fl_str_mv 2013-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/23871
Gillet, Nicolas A.; Gutiérrez, Gerónimo; Rodriguez, Sabrina M.; de Brogniez, Alix; Renotte, Nathelie; et al.; Massive depletion of bovine leukemia virus proviral clones located in genomic transcriptionally active sites during primary infection; Public Library of Science; Plos Pathogens; 9; 10; 10-2013; 1-13; e1003687
1553-7366
CONICET Digital
CONICET
url http://hdl.handle.net/11336/23871
identifier_str_mv Gillet, Nicolas A.; Gutiérrez, Gerónimo; Rodriguez, Sabrina M.; de Brogniez, Alix; Renotte, Nathelie; et al.; Massive depletion of bovine leukemia virus proviral clones located in genomic transcriptionally active sites during primary infection; Public Library of Science; Plos Pathogens; 9; 10; 10-2013; 1-13; e1003687
1553-7366
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1003687
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.ppat.1003687
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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