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

doi:10.1038/ncomms12412

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

Medicine, Infectious Diseases Division

Research output: Contribution to journal › Article › peer-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 language	English (US)
Article number	12412
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms12412
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ncomms12412

Cite this

Martinez-Picado, J., McLaren, P. J., Erkizia, I., Martin, M. P., Benet, S., Rotger, M., Dalmau, J., Ouchi, D., Wolinsky, S. M., Penugonda, S., Günthard, H. F., Fellay, J., Carrington, M., Izquierdo-Useros, N., & Telenti, A. (2016). Identification of siglec-1 null individuals infected with HIV-1. Nature communications, 7, Article 12412. https://doi.org/10.1038/ncomms12412

@article{851845ae349f449bbdeec23258a69159,

title = "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 {\^a} 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.",

author = "Javier Martinez-Picado and McLaren, {Paul J.} and Itziar Erkizia and Martin, {Maureen P.} and Susana Benet and Margalida Rotger and Judith Dalmau and Dan Ouchi and Wolinsky, {Steven M.} and Sudhir Penugonda and G{\"u}nthard, {Huldrych F.} and Jacques Fellay and Mary Carrington and Nuria Izquierdo-Useros and Amalio Telenti",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2016.",

year = "2016",

month = aug,

day = "11",

doi = "10.1038/ncomms12412",

language = "English (US)",

volume = "7",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Research",

}

TY - JOUR

T1 - Identification of siglec-1 null individuals infected with HIV-1

AU - Martinez-Picado, Javier

AU - McLaren, Paul J.

AU - Erkizia, Itziar

AU - Martin, Maureen P.

AU - Benet, Susana

AU - Rotger, Margalida

AU - Dalmau, Judith

AU - Ouchi, Dan

AU - Wolinsky, Steven M.

AU - Penugonda, Sudhir

AU - Günthard, Huldrych F.

AU - Fellay, Jacques

AU - Carrington, Mary

AU - Izquierdo-Useros, Nuria

AU - Telenti, Amalio

PY - 2016/8/11

Y1 - 2016/8/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84982102998&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84982102998&partnerID=8YFLogxK

U2 - 10.1038/ncomms12412

DO - 10.1038/ncomms12412

M3 - Article

C2 - 27510803

AN - SCOPUS:84982102998

SN - 2041-1723

VL - 7

JO - Nature communications

JF - Nature communications

M1 - 12412

ER -

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

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this