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
N1 - Funding Information:
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.
Publisher Copyright:
© The Author(s) 2016.
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.
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U2 - 10.1038/ncomms12412
DO - 10.1038/ncomms12412
M3 - Article
C2 - 27510803
AN - SCOPUS:84982102998
VL - 7
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 12412
ER -
