HIV-1 Disease Progression Is Associated with Bile-Salt Stimulated Lipase (BSSL) Gene Polymorphism

PLoS One

Michael W. T. Tanck¹  Neeltje A. Kootstra²  Angélique B. van 't Wout²  Martijn J. Stax³  Margreet Bakker³  Georgios Pollakis³  William A. Paxton³ 

[1] Department Clinical Epidemiology, Biostatistics and Bioinformatics (KEBB), Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands;Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and CINIMA at the Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands;Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA) at the Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands

关键词: HIV-1;    Variant genotypes;    Viral load;    T cells;    Men who have sex with men;    Milk;    AIDS;    Breast milk;   

DOI  :  10.1371/journal.pone.0032534

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Background DC-SIGN expressed by dendritic cells captures HIV-1 resulting in trans-infection of CD4+ T-lymphocytes. However, BSSL (bile-salt stimulated lipase) binding to DC-SIGN interferes with HIV-1 capture. DC-SIGN binding properties of BSSL associate with the polymorphic repeated motif of BSSL exon 11. Furthermore, BSSL binds to HIV-1 co-receptor CXCR4. We hypothesized that BSSL modulates HIV-1 disease progression and emergence of CXCR4 using HIV-1 (X4) variants. Results The relation between BSSL genotype and HIV-1 disease progression and emergence of X4 variants was studied using Kaplan Meier and multivariate Cox proportional hazard analysis in a cohort of HIV-1 infected men having sex with men (n = 334, with n = 130 seroconverters). We analyzed the association of BSSL genotype with set-point viral load and CD4 cell count, both pre-infection and post-infection at viral set-point. The number of repeats in BSSL exon 11 were highly variable ranging from 10 to 18 in seropositive individuals and from 5–17 in HRSN with 16 repeats being dominant (>80% carry at least one allele with 16 repeats). We defined 16 to 18 repeats as high (H) and less than 16 repeats as low (L) repeat numbers. Homozygosity for the high (H) repeat number BSSL genotype (HH) correlated with high CD4 cell numbers prior to infection (p = 0.007). In HIV-1 patients, delayed disease progression was linked to the HH BSSL genotype (RH = 0.462 CI = 0.282–0.757, p = 0.002) as was delayed emergence of X4 variants (RH = 0.525, 95% CI = 0.290–0.953, p = 0.034). The LH BSSL genotype, previously found to be associated with enhanced DC-SIGN binding of human milk, was identified to correlate with accelerated disease progression in our cohort of HIV-1 infected MSM (RH = 0.517, 95% CI = 0.328–0.818, p = 0.005). Conclusion We identify BSSL as a marker for HIV-1 disease progression and emergence of X4 variants. Additionally, we identified a relation between BSSL genotype and CD4 cell counts prior to infection.

【 授权许可】

CC BY