Genetic and Functional Analysis of HIV Type 1 nef Gene Derived from Long-Term Nonprogressor Children: Association of Attenuated Variants with Slow Progression to Pediatric AIDS

Autores
Corró, Guillermo; Rocco, Carlos Alberto; de Candia, Cristian Ariel; Catano, Gabriel; Turk, Gabriela Julia Ana; Mangano, Andrea Maria Mercedes; Aulicino, Paula; Bologna, Rosa; Sen, Luisa
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Among persons infected by HIV-1, the rate of progression to AIDS is multifactorial being affected by host and viral factors, including the HIV-encoded negative factor (Nef). Our aim was to define whether variations in the nef gene as well as its functions may be associated with slower HIV disease course in infected children. The proviral HIV-1 nef gene was cloned, sequenced, and compared in children with contrasting disease course: 10 long-term nonprogressors (LTNP) and six rapid progressor (RP). The CD4 and MHC-I down-modulation ability of nef alleles derived from LTNP and RP children was analyzed. We observed that only one of our 10 LTNP had a protective genetic background, and out of them, 40% had defective nef genes, carrying substitutions at the (AWLEAQ56–61) and the (Rxx22–24) domains, and that those alleles were unable of down-regulate CD4 and MHC-I. The emergence or presence of Nef L58V substitution was associated with viral attenuation, indicated by a reduction in HIV viral loads, a persistent preservation of CD4+ T cell counts, and lack of AIDS-related symptoms. Our results demonstrate that HIV-1 perinatally infected children carrying functionally defective nef HIV-1 strains have prolonged asymptomatic phases without therapy, suggesting a relevant role of CD4 and MHC-I down-modulation Nef domains on in vivo HIV-1 pathogenesis and pediatric immunodeficiency outcome.
Fil: Corró, Guillermo. 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: de Candia, Cristian Ariel. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia para el Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Catano, Gabriel. University of Texas; Estados Unidos
Fil: Turk, Gabriela Julia Ana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia para el Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mangano, Andrea Maria 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: Aulicino, Paula. 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: Bologna, Rosa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; 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 Pediatrics
Evolution
Nef
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:11336/29504
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/29504
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Genetic and Functional Analysis of HIV Type 1 nef Gene Derived from Long-Term Nonprogressor Children: Association of Attenuated Variants with Slow Progression to Pediatric AIDSCorró, GuillermoRocco, Carlos Albertode Candia, Cristian ArielCatano, GabrielTurk, Gabriela Julia AnaMangano, Andrea Maria MercedesAulicino, PaulaBologna, RosaSen, LuisaHiv PediatricsEvolutionNefhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Among persons infected by HIV-1, the rate of progression to AIDS is multifactorial being affected by host and viral factors, including the HIV-encoded negative factor (Nef). Our aim was to define whether variations in the nef gene as well as its functions may be associated with slower HIV disease course in infected children. The proviral HIV-1 nef gene was cloned, sequenced, and compared in children with contrasting disease course: 10 long-term nonprogressors (LTNP) and six rapid progressor (RP). The CD4 and MHC-I down-modulation ability of nef alleles derived from LTNP and RP children was analyzed. We observed that only one of our 10 LTNP had a protective genetic background, and out of them, 40% had defective nef genes, carrying substitutions at the (AWLEAQ56–61) and the (Rxx22–24) domains, and that those alleles were unable of down-regulate CD4 and MHC-I. The emergence or presence of Nef L58V substitution was associated with viral attenuation, indicated by a reduction in HIV viral loads, a persistent preservation of CD4+ T cell counts, and lack of AIDS-related symptoms. Our results demonstrate that HIV-1 perinatally infected children carrying functionally defective nef HIV-1 strains have prolonged asymptomatic phases without therapy, suggesting a relevant role of CD4 and MHC-I down-modulation Nef domains on in vivo HIV-1 pathogenesis and pediatric immunodeficiency outcome.Fil: Corró, Guillermo. 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: de Candia, Cristian Ariel. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia para el Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Catano, Gabriel. University of Texas; Estados UnidosFil: Turk, Gabriela Julia Ana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia para el Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mangano, Andrea Maria 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: Aulicino, Paula. 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: Bologna, Rosa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; 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 Liebert2012-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/29504Corró, Guillermo; Rocco, Carlos Alberto; de Candia, Cristian Ariel; Catano, Gabriel; Turk, Gabriela Julia Ana; et al.; Genetic and Functional Analysis of HIV Type 1 nef Gene Derived from Long-Term Nonprogressor Children: Association of Attenuated Variants with Slow Progression to Pediatric AIDS; Mary Ann Liebert; Aids Research and Human Retroviruses; 28; 12; 11-2012; 1617-16260889-2229enginfo:eu-repo/semantics/altIdentifier/url/http://online.liebertpub.com/doi/abs/10.1089/aid.2012.0020info:eu-repo/semantics/altIdentifier/doi/10.1089/aid.2012.0020info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:02:38Zoai:ri.conicet.gov.ar:11336/29504instacron: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:34982025-09-29 10:02:39.248CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Genetic and Functional Analysis of HIV Type 1 nef Gene Derived from Long-Term Nonprogressor Children: Association of Attenuated Variants with Slow Progression to Pediatric AIDS
title Genetic and Functional Analysis of HIV Type 1 nef Gene Derived from Long-Term Nonprogressor Children: Association of Attenuated Variants with Slow Progression to Pediatric AIDS
spellingShingle Genetic and Functional Analysis of HIV Type 1 nef Gene Derived from Long-Term Nonprogressor Children: Association of Attenuated Variants with Slow Progression to Pediatric AIDS
Corró, Guillermo
Hiv Pediatrics
Evolution
Nef
title_short Genetic and Functional Analysis of HIV Type 1 nef Gene Derived from Long-Term Nonprogressor Children: Association of Attenuated Variants with Slow Progression to Pediatric AIDS
title_full Genetic and Functional Analysis of HIV Type 1 nef Gene Derived from Long-Term Nonprogressor Children: Association of Attenuated Variants with Slow Progression to Pediatric AIDS
title_fullStr Genetic and Functional Analysis of HIV Type 1 nef Gene Derived from Long-Term Nonprogressor Children: Association of Attenuated Variants with Slow Progression to Pediatric AIDS
title_full_unstemmed Genetic and Functional Analysis of HIV Type 1 nef Gene Derived from Long-Term Nonprogressor Children: Association of Attenuated Variants with Slow Progression to Pediatric AIDS
title_sort Genetic and Functional Analysis of HIV Type 1 nef Gene Derived from Long-Term Nonprogressor Children: Association of Attenuated Variants with Slow Progression to Pediatric AIDS
dc.creator.none.fl_str_mv Corró, Guillermo
Rocco, Carlos Alberto
de Candia, Cristian Ariel
Catano, Gabriel
Turk, Gabriela Julia Ana
Mangano, Andrea Maria Mercedes
Aulicino, Paula
Bologna, Rosa
Sen, Luisa
author Corró, Guillermo
author_facet Corró, Guillermo
Rocco, Carlos Alberto
de Candia, Cristian Ariel
Catano, Gabriel
Turk, Gabriela Julia Ana
Mangano, Andrea Maria Mercedes
Aulicino, Paula
Bologna, Rosa
Sen, Luisa
author_role author
author2 Rocco, Carlos Alberto
de Candia, Cristian Ariel
Catano, Gabriel
Turk, Gabriela Julia Ana
Mangano, Andrea Maria Mercedes
Aulicino, Paula
Bologna, Rosa
Sen, Luisa
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Hiv Pediatrics
Evolution
Nef
topic Hiv Pediatrics
Evolution
Nef
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Among persons infected by HIV-1, the rate of progression to AIDS is multifactorial being affected by host and viral factors, including the HIV-encoded negative factor (Nef). Our aim was to define whether variations in the nef gene as well as its functions may be associated with slower HIV disease course in infected children. The proviral HIV-1 nef gene was cloned, sequenced, and compared in children with contrasting disease course: 10 long-term nonprogressors (LTNP) and six rapid progressor (RP). The CD4 and MHC-I down-modulation ability of nef alleles derived from LTNP and RP children was analyzed. We observed that only one of our 10 LTNP had a protective genetic background, and out of them, 40% had defective nef genes, carrying substitutions at the (AWLEAQ56–61) and the (Rxx22–24) domains, and that those alleles were unable of down-regulate CD4 and MHC-I. The emergence or presence of Nef L58V substitution was associated with viral attenuation, indicated by a reduction in HIV viral loads, a persistent preservation of CD4+ T cell counts, and lack of AIDS-related symptoms. Our results demonstrate that HIV-1 perinatally infected children carrying functionally defective nef HIV-1 strains have prolonged asymptomatic phases without therapy, suggesting a relevant role of CD4 and MHC-I down-modulation Nef domains on in vivo HIV-1 pathogenesis and pediatric immunodeficiency outcome.
Fil: Corró, Guillermo. 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: de Candia, Cristian Ariel. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia para el Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Catano, Gabriel. University of Texas; Estados Unidos
Fil: Turk, Gabriela Julia Ana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia para el Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mangano, Andrea Maria 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: Aulicino, Paula. 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: Bologna, Rosa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; 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 Among persons infected by HIV-1, the rate of progression to AIDS is multifactorial being affected by host and viral factors, including the HIV-encoded negative factor (Nef). Our aim was to define whether variations in the nef gene as well as its functions may be associated with slower HIV disease course in infected children. The proviral HIV-1 nef gene was cloned, sequenced, and compared in children with contrasting disease course: 10 long-term nonprogressors (LTNP) and six rapid progressor (RP). The CD4 and MHC-I down-modulation ability of nef alleles derived from LTNP and RP children was analyzed. We observed that only one of our 10 LTNP had a protective genetic background, and out of them, 40% had defective nef genes, carrying substitutions at the (AWLEAQ56–61) and the (Rxx22–24) domains, and that those alleles were unable of down-regulate CD4 and MHC-I. The emergence or presence of Nef L58V substitution was associated with viral attenuation, indicated by a reduction in HIV viral loads, a persistent preservation of CD4+ T cell counts, and lack of AIDS-related symptoms. Our results demonstrate that HIV-1 perinatally infected children carrying functionally defective nef HIV-1 strains have prolonged asymptomatic phases without therapy, suggesting a relevant role of CD4 and MHC-I down-modulation Nef domains on in vivo HIV-1 pathogenesis and pediatric immunodeficiency outcome.
publishDate 2012
dc.date.none.fl_str_mv 2012-11
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/11336/29504
Corró, Guillermo; Rocco, Carlos Alberto; de Candia, Cristian Ariel; Catano, Gabriel; Turk, Gabriela Julia Ana; et al.; Genetic and Functional Analysis of HIV Type 1 nef Gene Derived from Long-Term Nonprogressor Children: Association of Attenuated Variants with Slow Progression to Pediatric AIDS; Mary Ann Liebert; Aids Research and Human Retroviruses; 28; 12; 11-2012; 1617-1626
0889-2229
url http://hdl.handle.net/11336/29504
identifier_str_mv Corró, Guillermo; Rocco, Carlos Alberto; de Candia, Cristian Ariel; Catano, Gabriel; Turk, Gabriela Julia Ana; et al.; Genetic and Functional Analysis of HIV Type 1 nef Gene Derived from Long-Term Nonprogressor Children: Association of Attenuated Variants with Slow Progression to Pediatric AIDS; Mary Ann Liebert; Aids Research and Human Retroviruses; 28; 12; 11-2012; 1617-1626
0889-2229
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://online.liebertpub.com/doi/abs/10.1089/aid.2012.0020
info:eu-repo/semantics/altIdentifier/doi/10.1089/aid.2012.0020
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
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 13.070432

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