Dynamic disruptions in nuclear envelope architecture and integrity inducedby HIV-1 Vpr

Human immunodeficiency virus-1 (HIV-1) Vpr expression halts the proliferati on of human cells at or near the G(2) cell-cycle checkpoint. The transition from G(2) to mitosis is normally controlled by changes in the state of pho sphorylation and subcellular compartmentalization of key cell-cycle regulat ory proteins. In studies of the intracellular trafficking of these regulato rs, we unexpectedly found that wild-type Vpr, but not Vpr mutants impaired for G(2) arrest, induced transient, localized herniations in the nuclear en velope (NE). These herniations were associated with defects in the nuclear lamina. Intermittently, these herniations ruptured, resulting in the mixing of nuclear and cytoplasmic components. These Vpr-induced NE changes probab ly contribute to the observed cell-cycle arrest.