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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Detalles Bibliográficos
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
Descripción
Sumario: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.

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