Signatures of HIV-infected CD4 +T cell resistance to NK cell-mediated killing

Abstract BACKGROUND: In vitroexperiments in which HIV-infected CD4 +T cells are co-cultured with natural killer (NK) yield incomplete elimination of the infected cells. We therefore hypothesize that cell-intrinsic pathways differentially regulated to mediate resistance NK cell-mediated killing. METHODS: Mock-infected and HIV-89.6-infected from 6 HIV −donors were overnight +/− autologous Following co-culture, stained for surface exposed envelope protein using fluorescently conjugated antibodies. Fluorescence activated cell sorting was then used isolate uninfected cells, followed by bulk RNA-sequencing. Transcripts versus without compared. RESULTS: RNA-seq analysis survived co-culture revealed dozens expressed genes infected, but not This included upregulation interferon-stimulated genes, including PD-L1 (p adj=3×10 −6), NF-kB-related genes. Additional upregulated surviving c-Fos adj=1.9×10 −5), c-Jun adj=4.9×10 −8), cathepsin L adj=5×10 −3). CONCLUSIONS: NF-kB downregulated potentially through Vpu activity, normalized may be due targeting Vpu-mediated HLA-C downregulation. Deconvolution relative contributions specific genes/proteins target will reveal novel targets development therapeutics eliminate reservoir.