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

Javier Martinez-Picado (), Paul J. McLaren, Itziar Erkizia, Maureen P. Martin, Susana Benet, Margalida Rotger, Judith Dalmau, Dan Ouchi, Steven M. Wolinsky, Sudhir Penugonda, Huldrych F. Günthard, Jacques Fellay, Mary Carrington, Nuria Izquierdo-Useros () and Amalio Telenti ()
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Javier Martinez-Picado: AIDS Research Institute IrsiCaixa, Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Universitat Autònoma de Barcelona
Paul J. McLaren: National HIV and Retrovirology Laboratory, Public Health Agency of Canada
Itziar Erkizia: AIDS Research Institute IrsiCaixa, Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Universitat Autònoma de Barcelona
Maureen P. Martin: Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research
Susana Benet: AIDS Research Institute IrsiCaixa, Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Universitat Autònoma de Barcelona
Margalida Rotger: Institute of Microbiology, University Hospital Center and University of Lausanne
Judith Dalmau: AIDS Research Institute IrsiCaixa, Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Universitat Autònoma de Barcelona
Dan Ouchi: AIDS Research Institute IrsiCaixa, Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Universitat Autònoma de Barcelona
Steven M. Wolinsky: Northwestern University Feinberg School of Medicine
Sudhir Penugonda: Northwestern University Feinberg School of Medicine
Huldrych F. Günthard: University Hospital Zurich, University of Zurich
Jacques Fellay: School of Life Sciences, École Polytechnique Fédérale de Lausanne
Mary Carrington: Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research
Nuria Izquierdo-Useros: AIDS Research Institute IrsiCaixa, Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Universitat Autònoma de Barcelona
Amalio Telenti: Genomic Medicine, J. Craig Venter Institute

Nature Communications, 2016, vol. 7, issue 1, 1-7

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms12412

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