IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms12412.html
   My bibliography  Save this article

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

Author

Listed:
  • Javier Martinez-Picado

    (AIDS Research Institute IrsiCaixa, Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Universitat Autònoma de Barcelona
    Institució Catalana de Recerca i Estudis Avançats (ICREA)
    University of Vic-Central University of Catalonia (UVic-UCC))

  • Paul J. McLaren

    (National HIV and Retrovirology Laboratory, Public Health Agency of Canada
    University of Manitoba)

  • 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
    Institute of Medical Virology, University of Zurich)

  • Jacques Fellay

    (School of Life Sciences, École Polytechnique Fédérale de Lausanne
    Swiss Institute of Bioinformatics)

  • Mary Carrington

    (Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research
    Ragon Institute for MGH, MIT and Harvard)

  • 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)

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.

Suggested Citation

  • 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. Güntha, 2016. "Identification of Siglec-1 null individuals infected with HIV-1," Nature Communications, Nature, vol. 7(1), pages 1-7, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12412
    DOI: 10.1038/ncomms12412
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms12412
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms12412?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12412. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.