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

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.

• Authors: 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
• Journal: Nature communications (Nat Commun) Vol. 7 Pg. 12412 (08 11 2016) ISSN: 2041-1723 [Electronic] England
• PMID: 27510803 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• SIGLEC1 protein, human
• Sialic Acid Binding Ig-like Lectin 1

Topics

• Adult
• Alleles
• CD4-Positive T-Lymphocytes (metabolism)
• Cell Lineage
• Dendritic Cells (metabolism)
• Disease Progression
• Exome
• Exons
• Female
• Genetics, Population
• Genotype
• HIV Infections (genetics)
• HIV-1
• Heterozygote
• Homozygote
• Humans
• Leukocytes, Mononuclear (metabolism)
• Longitudinal Studies
• Male
• Middle Aged
• Prospective Studies
• Sialic Acid Binding Ig-like Lectin 1 (genetics)
• Switzerland
• United States