Title:
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Identification of Siglec-1 null individuals infected with HIV-1
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Author:
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Martínez Picado, Francisco Javier; McLaren, Paul J.; Erkizia, Itziar; Martin, Maureen P.; Benet, Susana; Rotger, Margalida; Dalmau, Judith; Ouchi, Dan; Wolinsky, Steven M.; Penugonda, Sudhir; Günthard, Huldrych F.; Fellay, Jacques; Carrington, Mary; Izquierdo Useros, Nuria; Telenti, Amalio
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Abstract:
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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 |
Abstract:
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Altres ajuts: GLD14/00271 |
Abstract:
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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. |
Subject(s):
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-Infeccions per VIH -VIH (Virus) -Siglec-1 |
Rights:
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open access
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https://creativecommons.org/licenses/by/4.0/ |
Document type:
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Article |
Published by:
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Share:
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Uri:
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https://ddd.uab.cat/record/174664
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