HIV-1 Vpr protein activates the NF-κB pathway to promote G2/M cell cycle arrest.

Abstract

Viral protein R (Vpr) plays an important role in the replication and pathogenesis of Human immunodeficiency virus type 1 (HIV-1). Some of the various functions attributed to Vpr, including the induction of G2/M cell cycle arrest, activating the NF-κB pathway, and promoting viral reverse transcription, might be interrelated. To test this hypothesis, a panel of Vpr mutants were investigated for their ability to induce G2/M arrest and to activate the NF-κB pathway. The results showed that the Vpr mutants that failed to activate NF-κB also lost the activity to induce G2/M arrest, which suggests that inducing G2/M arrest via Vpr depends at least partially on the activation of NF-κB. This latter possibility is supported by data showing that knocking down the key factors in the NF-κB pathway-p65, RelB, IKKα, or IKKβ-partially rescued the G2/M arrest induced by Vpr. Our results suggest that the NF-κB pathway is probably involved in Vpr-induced G2/M cell cycle arrest.