hiv-1 disease progression is associated with bile-salt stimulated lipase (bssl) gene polymorphismhiv - 1疾病进展与胆汁盐刺激脂肪酶(bssl)基因多态性.pdfVIP

HIV-1 Disease Progression Is Associated with Bile-Salt Stimulated Lipase (BSSL) Gene Polymorphism 1 2 ´ 2 3 1 Martijn J. Stax , Neeltje A. Kootstra , Angelique B. van ’t Wout , Michael W. T. Tanck , Margreet Bakker , 1 1 Georgios Pollakis , William A. Paxton * 1 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, 2 Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and CINIMA at the Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands, 3 Department Clinical Epidemiology, Biostatistics and Bioinformatics (KEBB), Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands Abstract 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,