Identification of Siglec-1 null individuals infected with HIV-1.
Javier Martinez-PicadoPaul J McLarenItziar ErkiziaMaureen P MartinSusana BenetMargalida RotgerJudith DalmauDan OuchiSteven M WolinskySudhir PenugondaHuldrych F GünthardJacques FellayMary CarringtonNuria Izquierdo-UserosAmalio TelentiPublished in: Nature communications (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 ∼1% 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.
Keyphrases
- hiv infected
- antiretroviral therapy
- hiv positive
- human immunodeficiency virus
- hiv testing
- hiv aids
- hepatitis c virus
- men who have sex with men
- magnetic resonance imaging
- cell surface
- computed tomography
- genome wide
- cell proliferation
- emergency department
- oxidative stress
- induced apoptosis
- dendritic cells
- immune response
- early onset
- insulin resistance
- high throughput
- skeletal muscle
- drug induced