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

28 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

Funding

The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), U01-AI35042, U01-AI35039, U01-AI35040, U01-AI35041 and UM1-AI35043, with additional co-funding from the National Cancer Institute (NCI). This project has been funded in part with federal funds from the Frederick National Laboratory for Cancer Research, under Contract No. HHSN261200800001E.

ASJC Scopus subject areas

  • General Physics and Astronomy
  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology

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