Bone marrow stromal antigen 2 (BST-2) genetic variants influence expression levels and disease outcome in HIV-1 chronically infected patients

Abstract BackgroundBone marrow stromal antigen 2 (BST-2) also known as Tetherin (CD317/HM1.24), is a host restriction factor that blocks the release of HIV-1 virions from infected cells. Previous studies reported that BST-2 genetic variants or single nucleotide polymorphims (SNPs) have a preventative role during HIV-1 infection. However, the influence of BST-2 SNPs on expression levels remains unknown. In this study, we investigated the inffluence of BST-2 SNPs on expression levels and disease outcome in HIV-1 subtype C chronically infected antiretroviral therapy naïve individuals.ResultsWe quantified BST-2 mRNA levels in peripheral blood mononuclear cells (PBMCs), determined BST-2 protein expression on the surface of CD4 + T cells using flow cytometry and genotyped single nucleotide polymorphisms (SNPs) rs919267, rs919266 and rs9576 using TaqMan assays from HIV-1 uninfected and infected participants. Determined the ability of plasma antibody levels to meadiate andibodydependenet cellular phagocytosis (ADCP) using gp120 consensus C and p24 subtype B/C protein. Fc receptor-mediated NK cell degranulation was evaluated as a surrogate for ADCC activity using plasma from HIV-1 positive participants. BST-2 mRNA expression levels in PBMCs and protein levels on CD4 + T cells were lower in HIV-1 infected compared to uninfected participants (p=0.075 and p=0.005, respectively). rs919267CT (p=0.042) and rs919267TT (p=0.045) were associated with lower BST-2 mRNA expression levels compared to rs919267CC in HIV-1 uninfected participants. In HIV-1 infected participants, rs919267CT associated with lower CD4 count, (p=0.003), gp120-IgG1 (p=0.040), gp120-IgG3 (p=0.016) levels and but higher viral load (p=0.001) while rs919267TT was associated with lower BST-2 mRNA levels (p=0.046), CD4 counts (p=0.001), gp120-IgG1 levels (p=0.033) but higher plasma viral load (p=0.007). Conversely, rs9576CA was associated with higher BST-2 mRNA expression levels (p=0.027), CD4 counts (p=0.079), gp120-IgG1 (p=0.009), -IgG3 (p=0.039) levels and but with lower viral load (p=0.037). However, there was not correlation between BST-2 SNPs, p24-IgG subclass, ADCC and ADCP activity. ConclusionOur findings show that bst- 2 SNPs mediate BST-2 expression and disease outcome, correlate with gp120-IgG1, gp120-IgG3 levels but p24-IgG levels, ADCC and ADCP activity. Future studies should investigate the role of BST-2 polymorphic variants on improving myeloid dentritic cell (DC) activation and MHC class II antigene presentation.