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

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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, Rel B, 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. 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, Rel B, 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.
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