Identification of Siglec-1 null individuals infected with HIV-1

Martínez Picado, Francisco Javier|||0000-0002-4916-2129; McLaren, Paul J.; Erkizia, Itziar|||0000-0003-1244-8972; Martin, Maureen P.; Benet, Susana|||0000-0002-2219-8826; Rotger, Margalida; Dalmau, Judith|||0000-0001-7513-3711; Ouchi, Dan|||0000-0002-8630-152X; Wolinsky, Steven M.; Penugonda, Sudhir; Günthard, Huldrych F.; Fellay, Jacques|||0000-0002-8240-939X; Carrington, Mary; Izquierdo Useros, Nuria|||0000-0002-1039-1821; Telenti, Amalio

Identification of Siglec-1 null individuals infected with HIV-1

Siglec-1/CD169 is a myeloid-cell surface receptor critical for HIV-1 capture and infection of bystander target cells. To dissect the role of SIGLEC1 in natura, we scan a large population genetic database and identify a loss-of-function variant (Glu88Ter) that is found in ∼1% of healthy people. Exome...

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Autores:	Martínez Picado, Francisco Javier\|\|\|0000-0002-4916-2129, McLaren, Paul J., Erkizia, Itziar\|\|\|0000-0003-1244-8972, Martin, Maureen P., Benet, Susana\|\|\|0000-0002-2219-8826, Rotger, Margalida, Dalmau, Judith\|\|\|0000-0001-7513-3711, Ouchi, Dan\|\|\|0000-0002-8630-152X, Wolinsky, Steven M., Penugonda, Sudhir, Günthard, Huldrych F., Fellay, Jacques\|\|\|0000-0002-8240-939X, Carrington, Mary, Izquierdo Useros, Nuria\|\|\|0000-0002-1039-1821, Telenti, Amalio
Tipo de recurso:	artículo
Fecha de publicación:	2016
País:	España
Institución:	Universitat Autònoma de Barcelona
Repositorio:	Dipòsit Digital de Documents de la UAB
Idioma:	inglés
OAI Identifier:	oai:ddd.uab.cat:174664
Acceso en línea:	https://ddd.uab.cat/record/174664 https://dx.doi.org/urn:doi:10.1038/ncomms12412
Access Level:	acceso abierto
Palabra clave:	Infeccions per VIH VIH (Virus) Siglec-1

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spelling	Identification of Siglec-1 null individuals infected with HIV-1Martínez Picado, Francisco Javier\|\|\|0000-0002-4916-2129McLaren, Paul J.Erkizia, Itziar\|\|\|0000-0003-1244-8972Martin, Maureen P.Benet, Susana\|\|\|0000-0002-2219-8826Rotger, MargalidaDalmau, Judith\|\|\|0000-0001-7513-3711Ouchi, Dan\|\|\|0000-0002-8630-152XWolinsky, Steven M.Penugonda, SudhirGünthard, Huldrych F.Fellay, Jacques\|\|\|0000-0002-8240-939XCarrington, MaryIzquierdo Useros, Nuria\|\|\|0000-0002-1039-1821Telenti, AmalioInfeccions per VIHVIH (Virus)Siglec-1Siglec-1/CD169 is a myeloid-cell surface receptor critical for HIV-1 capture and infection of bystander target cells. To dissect the role of SIGLEC1 in natura, we scan a large population genetic database and identify a loss-of-function variant (Glu88Ter) that is found in ∼1% of healthy people. Exome analysis and direct genotyping of 4,233 HIV-1-infected individuals reveals two Glu88Ter homozygous and 97 heterozygous subjects, allowing the analysis of ex vivo and in vivo consequences of SIGLEC1 loss-of-function. Cells from these individuals are functionally null or haploinsufficient for Siglec-1 activity in HIV-1 capture and trans-infection ex vivo. However, Siglec-1 protein truncation does not have a measurable impact on HIV-1 acquisition or AIDS outcomes in vivo. This result contrasts with the known in vitro functional role of Siglec-1 in HIV-1 trans-infection. Thus, it provides evidence that the classical HIV-1 infectious routes may compensate for the lack of Siglec-1 in fuelling HIV-1 dissemination within infected individuals. 22016-01-0120162016-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/174664https://dx.doi.org/urn:doi:10.1038/ncomms12412reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2013-49042-Ropen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1746642026-06-06T12:50:31Z
dc.title.none.fl_str_mv	Identification of Siglec-1 null individuals infected with HIV-1
title	Identification of Siglec-1 null individuals infected with HIV-1
spellingShingle	Identification of Siglec-1 null individuals infected with HIV-1 Martínez Picado, Francisco Javier\|\|\|0000-0002-4916-2129 Infeccions per VIH VIH (Virus) Siglec-1
title_short	Identification of Siglec-1 null individuals infected with HIV-1
title_full	Identification of Siglec-1 null individuals infected with HIV-1
title_fullStr	Identification of Siglec-1 null individuals infected with HIV-1
title_full_unstemmed	Identification of Siglec-1 null individuals infected with HIV-1
title_sort	Identification of Siglec-1 null individuals infected with HIV-1
dc.creator.none.fl_str_mv	Martínez Picado, Francisco Javier\|\|\|0000-0002-4916-2129 McLaren, Paul J. Erkizia, Itziar\|\|\|0000-0003-1244-8972 Martin, Maureen P. Benet, Susana\|\|\|0000-0002-2219-8826 Rotger, Margalida Dalmau, Judith\|\|\|0000-0001-7513-3711 Ouchi, Dan\|\|\|0000-0002-8630-152X Wolinsky, Steven M. Penugonda, Sudhir Günthard, Huldrych F. Fellay, Jacques\|\|\|0000-0002-8240-939X Carrington, Mary Izquierdo Useros, Nuria\|\|\|0000-0002-1039-1821 Telenti, Amalio
author	Martínez Picado, Francisco Javier\|\|\|0000-0002-4916-2129
author_facet	Martínez Picado, Francisco Javier\|\|\|0000-0002-4916-2129 McLaren, Paul J. Erkizia, Itziar\|\|\|0000-0003-1244-8972 Martin, Maureen P. Benet, Susana\|\|\|0000-0002-2219-8826 Rotger, Margalida Dalmau, Judith\|\|\|0000-0001-7513-3711 Ouchi, Dan\|\|\|0000-0002-8630-152X Wolinsky, Steven M. Penugonda, Sudhir Günthard, Huldrych F. Fellay, Jacques\|\|\|0000-0002-8240-939X Carrington, Mary Izquierdo Useros, Nuria\|\|\|0000-0002-1039-1821 Telenti, Amalio
author_role	author
author2	McLaren, Paul J. Erkizia, Itziar\|\|\|0000-0003-1244-8972 Martin, Maureen P. Benet, Susana\|\|\|0000-0002-2219-8826 Rotger, Margalida Dalmau, Judith\|\|\|0000-0001-7513-3711 Ouchi, Dan\|\|\|0000-0002-8630-152X Wolinsky, Steven M. Penugonda, Sudhir Günthard, Huldrych F. Fellay, Jacques\|\|\|0000-0002-8240-939X Carrington, Mary Izquierdo Useros, Nuria\|\|\|0000-0002-1039-1821 Telenti, Amalio
author2_role	author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Infeccions per VIH VIH (Virus) Siglec-1
topic	Infeccions per VIH VIH (Virus) Siglec-1
description	Siglec-1/CD169 is a myeloid-cell surface receptor critical for HIV-1 capture and infection of bystander target cells. To dissect the role of SIGLEC1 in natura, we scan a large population genetic database and identify a loss-of-function variant (Glu88Ter) that is found in ∼1% of healthy people. Exome analysis and direct genotyping of 4,233 HIV-1-infected individuals reveals two Glu88Ter homozygous and 97 heterozygous subjects, allowing the analysis of ex vivo and in vivo consequences of SIGLEC1 loss-of-function. Cells from these individuals are functionally null or haploinsufficient for Siglec-1 activity in HIV-1 capture and trans-infection ex vivo. However, Siglec-1 protein truncation does not have a measurable impact on HIV-1 acquisition or AIDS outcomes in vivo. This result contrasts with the known in vitro functional role of Siglec-1 in HIV-1 trans-infection. Thus, it provides evidence that the classical HIV-1 infectious routes may compensate for the lack of Siglec-1 in fuelling HIV-1 dissemination within infected individuals.
publishDate	2016
dc.date.none.fl_str_mv	2 2016-01-01 2016 2016-01-01
dc.type.none.fl_str_mv	Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://ddd.uab.cat/record/174664 https://dx.doi.org/urn:doi:10.1038/ncomms12412
url	https://ddd.uab.cat/record/174664 https://dx.doi.org/urn:doi:10.1038/ncomms12412
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.relation.none.fl_str_mv	Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2013-49042-R
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.source.none.fl_str_mv	reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona
instname_str	Universitat Autònoma de Barcelona
reponame_str	Dipòsit Digital de Documents de la UAB
collection	Dipòsit Digital de Documents de la UAB
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Identification of Siglec-1 null individuals infected with HIV-1

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