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Science 2 November 2001:
Vol. 294. no. 5544, pp. 1105 - 1108
DOI: 10.1126/science.1063957
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Reports

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

Carlos M. C. de Noronha,1 Michael P. Sherman,12 Harrison W. Lin,1 Marielle V. Cavrois,1 Robert D. Moir,4 Robert D. Goldman,4 Warner C. Greene123*

Human immunodeficiency virus-1 (HIV-1) Vpr expression halts the proliferation of human cells at or near the G2 cell-cycle checkpoint. The transition from G2 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 G2 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.

1 Gladstone Institute of Virology and Immunology,
2 Department of Medicine and
3 Department of Microbiology and Immunology, University of California, San Francisco, CA 94103, USA.
4 Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611, USA.
*   To whom correspondence should be addressed. E-mail: wgreene{at}gladstone.ucsf.edu

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