Martinez-Picado, JavierMclaren, Paul J.Erkizia, ItziarMartin, Maureen P.Benet, SusanaRotger, MargalidaDalmau, JudithOuchi, DanWolinsky, Steven M.Penugonda, SudhirGunthard, Huldrych F.Fellay, JacquesCarrington, MaryIzquierdo-Useros, NuriaTelenti, Amalio2016-10-182016-10-182016-10-18201610.1038/ncomms12412https://infoscience.epfl.ch/handle/20.500.14299/130410WOS:000381526300001Siglec-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 B1% 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.text::journal::journal article::research article