Effects of HIV protein Tat on macrophage transcriptome

Purpose: To investigate the impact of HIV protein Tat on macrophage transcriptome related to atherosclerosis development Methods: Peritoneal macrophages were isolated from myeloid specific IKKß deficient LDLR-/- (IKKß?MyeLDLR-/-) mice and their littermates (IKKßF/FLDLR-/-). Then the macrophages were treated with HIV protein Tat or control for 12 hr. Total RNA was extracted for RNAseq Results: HIV protein Tat treatment induces 2640 differentially expressed genes (DEGs) with false discovery rate (FDR) < 1 % and fold change > 3 in control macrophages. Those DEGs enriched in several biological processes that may contribute to atherogenesis. FAIME analysis demonstrated higher geneset scores of those GO terms in the Tat-treated macrophages from IKKßF/FLDLR-/- mice compared with the control ones. IKKß deletion resulted in loss of geneset score in the macrophages of IKKß?MyeLDLR-/- treated with HIV Tat. Conclusions: These results indicate that HIV protein Tat may affect many genes in macrophages related atherosclerosis development through IKKß signaling. Overall design: Macrophagic mRNA profiles of control and IKKß-deficient macrophages after 12-hour treatment of HIV protein Tat