miRNA expression changes in small intestinal lamina propria leukocyte samples during the course of SIV infection of rhesus macaques

This study describes differential miRNA expression in small intestinal lamina propria leukocyte samples longitudinally during the course of SIV infection of rhesus macaques. Notably, the T-cell activation associated miR-15b, miR-142-3p, miR-142-5p and miR-150 expression was significantly downregulated at 90 and 180DPI. Further, reporter and overexpression assays validated IRAK1 as a direct miR-150 target. Furthermore, IRAK1 protein levels were markedly elevated in intestinal LPLs and epithelium. Finally, blockade of CD8+ T-cell activation/proliferation with delta-9 tetrahydrocannabinol (9-THC) significantly prevented miR-150 downregulation and IRAK1 upregulation. Our findings suggest that miR-150 downregulation during T-cell activation may disrupt the translational control of IRAK1 facilitating persistent GI inflammation. We performed TaqMan Low Density Array based high throughput miRNA analysis longitudinally on intestinal lamina propria cells isolated before and thereafter at 21, 90 and 180 days post intravenous inoculation of rhesus macaques with 100TCID50 of SIV. microRNA reverse transcription and preamplification was performed according to the manufacturer’s recommendation. Data analysis was performed using RQ Manager 1.2.2 and DataAssist v3.01 software. Data was normalized to two endogenous controls, namely, snoU6 and RNU48. Due to the small sample size and exploratory nature of the study, multiple comparisons correction was not performed.