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, Amalio Telenti

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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 â 1/41% 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.

Original languageEnglish (US)
Article number12412
JournalNature communications
Volume7
DOIs
StatePublished - Aug 11 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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