Dynamic Disruptions in Nuclear Envelope Architecture and Integrity Induced by HIV-1 Vpr

Abstract

Human immunodeficiency virus–1 (HIV-1) Vpr expression halts the proliferation 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 phosphorylation and subcellular compartmentalization of key cell-cycle regulatory proteins. In studies of the intracellular trafficking of these regulators, we unexpectedly found that wild-type Vpr, but not Vpr mutants impaired for G 2 arrest, induced transient, localized herniations in the nuclear envelope (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 probably contribute to the observed cell-cycle arrest.