eLife https://doi.org/10.7554/eLife.41930 (5 Feb. 2019)

Vpu is an accessory protein of human immunodeficiency virus type 1 that serves well-described immunomodulatory functions mainly via its antagonism of the host cell–expressed restriction factor tetherin. In eLife, Sauter and colleagues compare wild-type and mutant versions of Vpu to investigate other potential immunomodulatory effects. Functional Vpu imposes considerable suppression of CD4+ T cell transcription, and this is independent of any effects on tetherin. In particular, many genes controlled by the transcription factor NF-κB — including those encoding the proinflammatory cytokines IL-6 and type 1 interferons and chemokines such as CXCL10 — are selectively suppressed. Although the mechanistic details of how Vpu impairs NF-κB activity remain to be determined, these findings demonstrate that Vpu has a much wider range of immunomodulatory effects than previously appreciated.