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 - © The Author(s) 2016. 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 - © The Author(s) 2016. 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.
U2 - 10.1038/ncomms12412
DO - 10.1038/ncomms12412
M3 - Article
SN - 2041-1723
VL - 7
JO - Nature Communications
JF - Nature Communications
M1 - 12412
ER -
