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

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Martinez-Picado 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,
Project Swiss HIV Cohort Study (SHCS)
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Original article (peer-reviewed)

Journal Nature communications
Volume (Issue) 7
Page(s) 12412 - 12412
Title of proceedings Nature communications
DOI 10.1038/ncomms12412

Open Access

URL http://doi.org/10.1038/ncomms12412
Type of Open Access Publisher (Gold Open Access)

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.
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