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Journal of Virology, April 1999, p. 3236-3245, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Mutational Analysis of Vpr-Induced G2 Arrest, Nuclear Localization, and Cell Death in Fission Yeast

Mingzhong Chen,1 Robert T. Elder,1 Min Yu,1 Maurice G. O'Gorman,2 Luc Selig,3 Richard Benarous,3 Ayumu Yamamoto,4 and Yuqi Zhao1,2,5,*

Children's Memorial Institute of Education and Research1 and Departments of Pediatrics2 and Microbiology-Immunology,5 Northwestern University Medical School, Chicago, Illinois 60614; Laboratoire de Génétique Moléculaire des Interactions Protéiques, INSERM U332, ICGM, Université Paris V, 75014 Paris, France3; and Communication Research Laboratory, Kansai Advanced Research Center, Kobe, Japan4

Received 11 August 1998/Accepted 26 December 1998

Cell cycle G2 arrest, nuclear localization, and cell death induced by human immunodeficiency virus type 1 Vpr were examined in fission yeast by using a panel of Vpr mutations that have been studied previously in human cells. The effects of the mutations on Vpr functions were highly similar between fission yeast and human cells. Consistent with mammalian cell studies, induction of cell cycle G2 arrest by Vpr was found to be independent of nuclear localization. In addition, G2 arrest was also shown to be independent of cell killing, which only occurred when the mutant Vpr localized to the nucleus. The C-terminal end of Vpr is crucial for G2 arrest, the N-terminal alpha -helix is important for nuclear localization, and a large part of the Vpr protein is responsible for cell killing. It is evident that the overall structure of Vpr is essential for these cellular effects, as N- and C-terminal deletions affected all three cellular functions. Furthermore, two single point mutations (H33R and H71R), both of which reside at the end of each alpha -helix, disrupted all three Vpr functions, indicating that these two mutations may have strong effects on the overall Vpr structure. The similarity of the mutant effects on Vpr function in fission yeast and human cells suggests that fission yeast can be used as a model system to evaluate these Vpr functions in naturally occurring viral isolates.

* Corresponding author. Mailing address: 2430 N. Halsted St., #218, Chicago, IL 60614. Phone: (773) 880-6608. Fax: (773) 880-6609. E-mail: yzhao{at}nwu.edu.

Journal of Virology, April 1999, p. 3236-3245, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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