Vpr induces a G2 cell cycle arrest and eventually apoptosis. (A) In uninfected cells Polo like kinase-1 (Plk1) activates the Mitosis Promoting Factor (MPF) both directly and indirectly by inhibiting the Wee1 and the Mut1 kinases. Cdc25 proteins are also involved in MPF activation via a positive retroactive loop. In normal cells, MPF activation leads to mitosis; in non-viable cells, mitosis acts as a checkpoint and cells die by apoptosis. (B) In HIV-1 infected cells, Vpr expression induces the relocalization of Plk1 and form a ternary complex with 14-3-3 and Cdc25. MPF cannot be activated, and consequently cells arrest in G2 phase. Non-viable (polyploid) cells transiently accumulate. If the cell-cycle arrest is prolonged, cells die by necrosis.