Insights into the role of HIV-1 Vpu in modulation of NF-ĸB signaling pathways.

HIV-1 inhibits the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) to prevent the induction of a proinflammatory state but also activates the NF-κB pathway to promote viral transcription. Thus, optimal regulation of this pathway is important for the viral life cycle. In recent work, Pickering et al (3) demonstrate that HIV-1 viral protein U has contrasting effects on the two distinct paralogs of β-transducin repeat-containing protein (β-TrCP1 and β-TrCP2) and that this interaction has important implications for the regulation of both the canonical and non-canonical NF-κB pathways. Additionally, the authors identified the viral requirements for the dysregulation of β-TrCP. In this commentary, we discuss how these findings further our understanding of how the NF-κB pathway functions during viral infection.