HIV-1 Vpr induces an NFAT-controlled transcriptional program in primary CD4+ T cells.

HIV-1 Vpr has a major impact on the cellular transcriptome and proteome. Although Vpr is known to stimulate the nuclear factor of activated T cells (NFAT), it remained unclear to what extent transcriptional changes induced by Vpr are governed by NFAT. We, therefore, performed RNA sequencing and transcription factor network analyses of primary CD4+ T cells infected with HIV-1 harboring an intact or defective IMPORTANCE: The HIV-1 accessory protein Vpr is known for its profound effect on the host proteome. It degrades many cellular proteins, including transcription factors and DNA-associated proteins. In addition, Vpr activates the nuclear factor of activated T cells (NFAT), a key transcription factor in T cells. However, it has remained unclear to what extent Vpr and consequently NFAT control changes in the transcriptome of HIV-1-infected primary CD4+ T cells. In this study, we show that Vpr significantly alters the transcriptome of CD4+ T cells, with almost half of the deregulated genes being under NFAT control. These changes involve pathways associated with increased immune activation and cell cycle regulation, shedding light on how Vpr contributes to CD4+ T cell depletion and HIV-1 pathogenesis.