APOBEC3-mediated editing in HIV type 1 from pediatric patients and its association with APOBEC3G/CUL5 polymorphisms and Vif variability

Autores
de Maio, Federico Andres; Rocco, Carlos Alberto; Aulicino, Paula; Bologna, Rosa; Mangano, Andrea María Mercedes; Sen, Luisa
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The APOBEC3 proteins are cytidine deaminases that can introduce G→A mutations in the HIV-1 plus DNA strand. This editing process may inhibit virus replication through lethal mutagenesis (hypermutation), but could also contribute to viral diversification leading to the emergence of escape forms. The HIV-1 Vif protein has the capacity to counteract APOBEC3 factors by recruiting a CUL5-based ubiquitin ligase complex that determines their proteasomal degradation. In this work, we analyzed the APOBEC3-mediated editing in proviral HIV-1 from perinatally infected children (n=93) in order to explore its association with polymorphisms of APOBEC3G and CUL5 genes (APOBEC3G H186R, APOBEC3G C40693T, and CUL5 SNP6), the Vif protein variability, and also the time to AIDS development. To calculate the level of editing, we have developed an index exploiting the properties of a region within the HIV-1 pol gene that includes the central polypurine tract (cPPT). We detected a reduced editing associated with the CUL5 SNP6 minor allele and also with certain Vif variants (mutations at sites 46, 122, and 160), although we found no evidence supporting an impact of APOBEC3 activity on disease progression. Thus, our findings suggest that APOBEC3-mediated editing of HIV-1 could be modulated by host and virus genetic characteristics in the context of pediatric infection.
Fil: de Maio, Federico Andres. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Biología Celular y Retrovirus; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rocco, Carlos Alberto. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Biología Celular y Retrovirus; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Aulicino, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Biología Celular y Retrovirus; Argentina
Fil: Bologna, Rosa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Mangano, Andrea María Mercedes. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Biología Celular y Retrovirus; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sen, Luisa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Biología Celular y Retrovirus; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
HIV-1
APOBEC3
VIF
EDITING
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/195810
Acceder
id CONICETDig_83f425da8c52eb4bae1d5c28a6f08918
oai_identifier_str oai:ri.conicet.gov.ar:11336/195810
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling APOBEC3-mediated editing in HIV type 1 from pediatric patients and its association with APOBEC3G/CUL5 polymorphisms and Vif variabilityde Maio, Federico AndresRocco, Carlos AlbertoAulicino, PaulaBologna, RosaMangano, Andrea María MercedesSen, LuisaHIV-1APOBEC3VIFEDITINGhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The APOBEC3 proteins are cytidine deaminases that can introduce G→A mutations in the HIV-1 plus DNA strand. This editing process may inhibit virus replication through lethal mutagenesis (hypermutation), but could also contribute to viral diversification leading to the emergence of escape forms. The HIV-1 Vif protein has the capacity to counteract APOBEC3 factors by recruiting a CUL5-based ubiquitin ligase complex that determines their proteasomal degradation. In this work, we analyzed the APOBEC3-mediated editing in proviral HIV-1 from perinatally infected children (n=93) in order to explore its association with polymorphisms of APOBEC3G and CUL5 genes (APOBEC3G H186R, APOBEC3G C40693T, and CUL5 SNP6), the Vif protein variability, and also the time to AIDS development. To calculate the level of editing, we have developed an index exploiting the properties of a region within the HIV-1 pol gene that includes the central polypurine tract (cPPT). We detected a reduced editing associated with the CUL5 SNP6 minor allele and also with certain Vif variants (mutations at sites 46, 122, and 160), although we found no evidence supporting an impact of APOBEC3 activity on disease progression. Thus, our findings suggest that APOBEC3-mediated editing of HIV-1 could be modulated by host and virus genetic characteristics in the context of pediatric infection.Fil: de Maio, Federico Andres. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Biología Celular y Retrovirus; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rocco, Carlos Alberto. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Biología Celular y Retrovirus; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Aulicino, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Biología Celular y Retrovirus; ArgentinaFil: Bologna, Rosa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Mangano, Andrea María Mercedes. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Biología Celular y Retrovirus; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sen, Luisa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Biología Celular y Retrovirus; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaMary Ann Liebert2012-06info: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/11336/195810de Maio, Federico Andres; Rocco, Carlos Alberto; Aulicino, Paula; Bologna, Rosa; Mangano, Andrea María Mercedes; et al.; APOBEC3-mediated editing in HIV type 1 from pediatric patients and its association with APOBEC3G/CUL5 polymorphisms and Vif variability; Mary Ann Liebert; Aids Research and Human Retroviruses; 28; 6; 6-2012; 619-6270889-2229CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.liebertpub.com/doi/10.1089/aid.2011.0291info:eu-repo/semantics/altIdentifier/doi/10.1089/aid.2011.0291info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:01:55Zoai:ri.conicet.gov.ar:11336/195810instacron: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:34982025-09-10 13:01:55.683CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv APOBEC3-mediated editing in HIV type 1 from pediatric patients and its association with APOBEC3G/CUL5 polymorphisms and Vif variability
title APOBEC3-mediated editing in HIV type 1 from pediatric patients and its association with APOBEC3G/CUL5 polymorphisms and Vif variability
spellingShingle APOBEC3-mediated editing in HIV type 1 from pediatric patients and its association with APOBEC3G/CUL5 polymorphisms and Vif variability
de Maio, Federico Andres
HIV-1
APOBEC3
VIF
EDITING
title_short APOBEC3-mediated editing in HIV type 1 from pediatric patients and its association with APOBEC3G/CUL5 polymorphisms and Vif variability
title_full APOBEC3-mediated editing in HIV type 1 from pediatric patients and its association with APOBEC3G/CUL5 polymorphisms and Vif variability
title_fullStr APOBEC3-mediated editing in HIV type 1 from pediatric patients and its association with APOBEC3G/CUL5 polymorphisms and Vif variability
title_full_unstemmed APOBEC3-mediated editing in HIV type 1 from pediatric patients and its association with APOBEC3G/CUL5 polymorphisms and Vif variability
title_sort APOBEC3-mediated editing in HIV type 1 from pediatric patients and its association with APOBEC3G/CUL5 polymorphisms and Vif variability
dc.creator.none.fl_str_mv de Maio, Federico Andres
Rocco, Carlos Alberto
Aulicino, Paula
Bologna, Rosa
Mangano, Andrea María Mercedes
Sen, Luisa
author de Maio, Federico Andres
author_facet de Maio, Federico Andres
Rocco, Carlos Alberto
Aulicino, Paula
Bologna, Rosa
Mangano, Andrea María Mercedes
Sen, Luisa
author_role author
author2 Rocco, Carlos Alberto
Aulicino, Paula
Bologna, Rosa
Mangano, Andrea María Mercedes
Sen, Luisa
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv HIV-1
APOBEC3
VIF
EDITING
topic HIV-1
APOBEC3
VIF
EDITING
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The APOBEC3 proteins are cytidine deaminases that can introduce G→A mutations in the HIV-1 plus DNA strand. This editing process may inhibit virus replication through lethal mutagenesis (hypermutation), but could also contribute to viral diversification leading to the emergence of escape forms. The HIV-1 Vif protein has the capacity to counteract APOBEC3 factors by recruiting a CUL5-based ubiquitin ligase complex that determines their proteasomal degradation. In this work, we analyzed the APOBEC3-mediated editing in proviral HIV-1 from perinatally infected children (n=93) in order to explore its association with polymorphisms of APOBEC3G and CUL5 genes (APOBEC3G H186R, APOBEC3G C40693T, and CUL5 SNP6), the Vif protein variability, and also the time to AIDS development. To calculate the level of editing, we have developed an index exploiting the properties of a region within the HIV-1 pol gene that includes the central polypurine tract (cPPT). We detected a reduced editing associated with the CUL5 SNP6 minor allele and also with certain Vif variants (mutations at sites 46, 122, and 160), although we found no evidence supporting an impact of APOBEC3 activity on disease progression. Thus, our findings suggest that APOBEC3-mediated editing of HIV-1 could be modulated by host and virus genetic characteristics in the context of pediatric infection.
Fil: de Maio, Federico Andres. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Biología Celular y Retrovirus; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rocco, Carlos Alberto. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Biología Celular y Retrovirus; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Aulicino, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Biología Celular y Retrovirus; Argentina
Fil: Bologna, Rosa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Mangano, Andrea María Mercedes. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Biología Celular y Retrovirus; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sen, Luisa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Biología Celular y Retrovirus; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description The APOBEC3 proteins are cytidine deaminases that can introduce G→A mutations in the HIV-1 plus DNA strand. This editing process may inhibit virus replication through lethal mutagenesis (hypermutation), but could also contribute to viral diversification leading to the emergence of escape forms. The HIV-1 Vif protein has the capacity to counteract APOBEC3 factors by recruiting a CUL5-based ubiquitin ligase complex that determines their proteasomal degradation. In this work, we analyzed the APOBEC3-mediated editing in proviral HIV-1 from perinatally infected children (n=93) in order to explore its association with polymorphisms of APOBEC3G and CUL5 genes (APOBEC3G H186R, APOBEC3G C40693T, and CUL5 SNP6), the Vif protein variability, and also the time to AIDS development. To calculate the level of editing, we have developed an index exploiting the properties of a region within the HIV-1 pol gene that includes the central polypurine tract (cPPT). We detected a reduced editing associated with the CUL5 SNP6 minor allele and also with certain Vif variants (mutations at sites 46, 122, and 160), although we found no evidence supporting an impact of APOBEC3 activity on disease progression. Thus, our findings suggest that APOBEC3-mediated editing of HIV-1 could be modulated by host and virus genetic characteristics in the context of pediatric infection.
publishDate 2012
dc.date.none.fl_str_mv 2012-06
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/11336/195810
de Maio, Federico Andres; Rocco, Carlos Alberto; Aulicino, Paula; Bologna, Rosa; Mangano, Andrea María Mercedes; et al.; APOBEC3-mediated editing in HIV type 1 from pediatric patients and its association with APOBEC3G/CUL5 polymorphisms and Vif variability; Mary Ann Liebert; Aids Research and Human Retroviruses; 28; 6; 6-2012; 619-627
0889-2229
CONICET Digital
CONICET
url http://hdl.handle.net/11336/195810
identifier_str_mv de Maio, Federico Andres; Rocco, Carlos Alberto; Aulicino, Paula; Bologna, Rosa; Mangano, Andrea María Mercedes; et al.; APOBEC3-mediated editing in HIV type 1 from pediatric patients and its association with APOBEC3G/CUL5 polymorphisms and Vif variability; Mary Ann Liebert; Aids Research and Human Retroviruses; 28; 6; 6-2012; 619-627
0889-2229
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.liebertpub.com/doi/10.1089/aid.2011.0291
info:eu-repo/semantics/altIdentifier/doi/10.1089/aid.2011.0291
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Mary Ann Liebert
publisher.none.fl_str_mv Mary Ann Liebert
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 12.993085

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