Quantitative expression analysis of rhesus macaque MHC alleles (APP3P.102)

Abstract

Abstract The relevance of MHC genes to HIV infection and disease progression is well established, and nonhuman primates are the most important model for AIDS vaccine research and development. However, due to the structural and sequence complexity of the macaque MHC, the expression changes across this complex region have not been determined accurately. We are developing a strategy for accurately quantifying rhesus MHC allele expression. Our strategy leverages a large collection of full-length rhesus MHC genomic sequences and a custom-developed computational pipeline, and only requires regular macaque RNA-seq data from users. We used this technique to analyze RNA-seq data collected from normal rhesus macaque tissue samples and PBMC samples from acutely infected rhesus macaques. We show that the expression of both MHC class I and class II genes was highly tissue specific, and multiple class I alleles were expressed within a single tissue. Compared to animal matched baseline PBMC samples, there was an overall increase in the expression of class I alleles in acutely infected rhesus macaques, as early as 3 days post infection. Both up-regulation and down-regulation of class II gene expression in PBMC samples was also observed during acute SIV infection. This study presents for the first time a systematic quantification of macaque MHC allele expression. The results may reveal limits in our understanding to fully account for the impact of MHC expression on immunological outcomes.