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To dissect the role of <jats:italic>SIGLEC1 in natura<\/jats:italic>, we scan a large population genetic database and identify a loss-of-function variant (Glu88Ter) that is found in \u223c1% 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 <jats:italic>ex vivo<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> consequences of <jats:italic>SIGLEC1<\/jats:italic> loss-of-function. Cells from these individuals are functionally null or haploinsufficient for Siglec-1 activity in HIV-1 capture and <jats:italic>trans<\/jats:italic>-infection <jats:italic>ex vivo<\/jats:italic>. However, Siglec-1 protein truncation does not have a measurable impact on HIV-1 acquisition or AIDS outcomes <jats:italic>in vivo<\/jats:italic>. This result contrasts with the known <jats:italic>in vitro<\/jats:italic> functional role of Siglec-1 in HIV-1 <jats:italic>trans<\/jats:italic>-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.<\/jats:p>","DOI":"10.1038\/ncomms12412","type":"journal-article","created":{"date-parts":[[2016,8,11]],"date-time":"2016-08-11T10:47:53Z","timestamp":1470912473000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Identification of Siglec-1 null individuals infected with HIV-1"],"prefix":"10.1038","volume":"7","author":[{"given":"Javier","family":"Martinez-Picado","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"McLaren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itziar","family":"Erkizia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen P.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Benet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margalida","family":"Rotger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Dalmau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Ouchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Wolinsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudhir","family":"Penugonda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huldrych F.","family":"G\u00fcnthard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8240-939X","authenticated-orcid":false,"given":"Jacques","family":"Fellay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Carrington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Izquierdo-Useros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6290-7677","authenticated-orcid":false,"given":"Amalio","family":"Telenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,8,11]]},"reference":[{"key":"BFncomms12412_CR1","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1126\/science.1352913","volume":"257","author":"PU Cameron","year":"1992","unstructured":"Cameron, P. 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