HIV-1 Vpu exerts broad immunosuppressive effects by inhibiting NF-κB-dependent gene expression

Using an unbiased RNA sequencing approach of primary CD4+ T cells infected with three wild type primary HIV-1 isolates and selective mutants thereof, Langer et al. show that the HIV-1 accessory protein Vpu exerts broad immunosuppressive effects, inhibiting the induction of innate and adaptive immune responses. Transcription factor network analyses reveal that Vpu suppresses the expression of NF‑κB rather than IRF3 target genes. As a result, Vpu impairs the production of pro-inflammatory cytokines such as IFNβ, CXCL10 and IL-6.