Variation in Six Innate Imune Genes Does Not Determine Protective Immunity Against SIV in Rhesus Macaques

摘要

HIV vaccine trials in humans have shown variability in vaccine responses among individuals. The SIV:macaque model can be used to understand the outcome of HIV vaccine trials in humans, specifically, the role of the innate immune system in inducing protective immunity. CXCL13, CCL20, CCL1, CCL2, CCL5, and TRIM5α, molecules of the innate immune system, were selected as part of a study into the relationship between these molecules and vaccine response. Sequence variation in the innate immune genes was determined in 25 rhesus macaques that were part of a SIV vaccine trial, a multiple low dose exposure study, or a control group. PCR primers were designed, based on the published rhesus macaque genome, to amplify approximately 2 kilobases of promoter region and the exons of the genes. Each amplicon was sequenced in at least 8 animals, and the sequences were visually screened for single nucleotide polymorphisms (SNPs). Numerous SNPs were detected in all of these genes. Statistical analysis showed that there was no correlation between polymorphisms in these genes and protection against SIV challenge. Copy number variation (CNV) was also examined in these genes using either custom TaqMan copy number assays or SYBR Green assays and quantitative real-time PCR. The results of the TaqMan assay indicate that CXCL13 demonstrates CNV. Genetic variation in these innate immune genes is likely not important in rhesus macaque response to SIV challenge, although larger studies are needed to provide more definitive results. The publicudHealth significance of this study is that understanding genetic factors that influence macaque responses to vaccination or SIV challenge will help us to understand HIV in humans with the goal of developing a more effective vaccine and the ability to predict individual’s susceptibility to disease or response to vaccination.ud