Identification of Siglec-1 null individuals infected with HIV-1
Martínez Picado, Francisco Javier (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
McLaren, Paul J. (National HIV and Retrovirology Laboratory (Winnipeg, Canadà))
Erkizia, Itziar (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Martin, Maureen P. (Frederick National Laboratory for Cancer Research (Maryland, Estats Units d'Amèrica))
Benet, Susana (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Rotger, Margalida (University of Lausanne (Suïssa))
Dalmau, Judith (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Ouchi, Dan (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Wolinsky, Steven M. (Northwestern University Feinberg School of Medicine (Chicago, Estats Units d'Amèrica))
Penugonda, Sudhir (Northwestern University Feinberg School of Medicine (Chicago, Estats Units d'Amèrica))
Günthard, Huldrych F. (University Hospital Zurich (Suïssa))
Fellay, Jacques (École Polytechnique Fédérale de Lausanne (Suïssa))
Carrington, Mary (Frederick National Laboratory for Cancer Research (Maryland, Estats Units d'Amèrica))
Izquierdo Useros, Nuria (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Telenti, Amalio (J. Craig Venter Institute (La Jolla, Estats Units d'Amèrica))

Date:	2016
Abstract:	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.
Grants:	Ministerio de Ciencia e Innovación SAF2013-49042-R
Note:	Altres ajudes: Gilead Fellowship Program GLD1400271; Mathilde Krim Fellowship in basic biomedical research 10867; SHCS Project number 717; Swiss National Science Foundation (Grant Number 148522); NIAID U01-AI35042, U01-AI35039, U01-AI35040, U01-AI35041 i UM1-AI3504; Frederick National Laboratory for Cancer Research contract HHSN261200800001E
Note:	Altres ajuts: GLD14/00271
Rights:	Aquest 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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Infeccions per VIH ; VIH (Virus) ; Siglec-1
Published in:	Nature communications, Vol. 7 Núm. 12412 (August 2016) , ISSN 2041-1723

DOI: 10.1038/ncomms12412
PMID: 27510803

7 p, 617.5 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles