Suchergebnisse

© 2014 Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US. Background.ZNRD1 was identified as a host protein required for the completion of the human immunodeficiency virus (HIV) lifecycle in a genome-wide screen using small interfering RNA gene silencing. Subsequently, a genome-wide association study (GWAS) of host determinants for HIV-1 disease identified an association of single nucleotide polymorphisms (SNPs) in the ZNRD1 region with CD4+T-cell depletion. Methods.We investigated the effects of SNPs in the ZNRD1 region on human immunodeficiency virus type 1 (HIV-1) infection and progression to clinical outcomes in 5 US-based HIV-1 longitudinal cohorts consisting of men who have sex with men, males with hemophilia, and injection drug users (IDUs) (n = 1865). SNP function was evaluated by electrophoretic mobility shift assay and promoter luciferase assay. Results.A haplotype in the ZNRD1 gene showed significant association with a 35% decreased risk of HIV-1 acquisition (OR = 0.65, 95% CI,. 47-.89), independent of HLA-C rs9264942, in European Americans. The SNP rs3132130 tagging this haplotype, located in the ZNRD1 5′ upstream region, caused a loss of nuclear factor binding and decrease in ZNRD1 promoter activity. ZNRD1 variants also affected HIV-1 disease progression in European- and African-American cohorts. Conclusions.This study provides novel evidence that ZNRD1 polymorphism may confer host resistance to HIV-1 acquisition.