Impaired CD4+ T cell differentiation in HIV-1 infected patients receiving early anti-retroviral therapy

Abstract

Differentiation of CD4+ T naïve (T_N) into central memory (T_CM) cells involves extensive molecular processes. We compared the transcriptomes of CD4+ T_N and T_CM cells from HIV-1 infected patients receiving early anti-retroviral therapy (ART; EA; n = 13) and controls (n = 15). Comparison of protein coding genes between T_CM and T_N revealed 533 and 82 differentially expressed genes (DEGs) in controls and EA, respectively. A high degree of transcriptional complexity was detected during transition of CD4+ T_N to T_CM cells in controls involving 70 TFs, 20 master regulators of T cell differentiation (TBX21, GATA3, RARA, FOXP3, RORC); in EA only 7 TFs were modulated with expression of several master regulators remaining unchanged during differentiation. Analysis of interactions between modulated TFs and target genes revealed important regulatory interactions missing in EA group. We conclude that T cell differentiation in EA patients is impaired due to reduced modulation of genes involved in transition from CD4+ T_N to T_CM cells.

Keywords: CD4+ T cell differentiation; CD4+ Th signatures; Chemokine receptors; Early ART; HIV-1; RNA-seq; Transcription factors.