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Science 10 July 1998:
Vol. 281. no. 5374, pp. 266 - 269
DOI: 10.1126/science.281.5374.266
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Reports

Cell Cycle Arrest by Vpr in HIV-1 Virions and Insensitivity to Antiretroviral Agents

Betty Poon, Kathie Grovit-Ferbas, Sheila A. Stewart, Irvin S. Y. Chen *

Expression of human immunodeficiency virus-type 1 (HIV-1) Vpr after productive infection of T cells induces cell cycle arrest in the G2 phase of the cell cycle. In the absence of de novo expression, HIV-1 Vpr packaged into virions still induced cell cycle arrest. Naturally noninfectious virus or virus rendered defective for infection by reverse transcriptase or protease inhibitors were capable of inducing Vpr-mediated cell cycle arrest. These results suggest a model whereby both infectious and noninfectious virions in vivo, such as those surrounding follicular dendritic cells, participate in immune suppression.

B. Poon, S. A. Stewart, I. S. Y. Chen, Department of Microbiology and Immunology and Medicine, UCLA AIDS Institute, and Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, CA 90095, USA. K. Grovit-Ferbas, Department of Medicine, UCLA AIDS Institute, UCLA School of Medicine, and West Los Angeles VAMC, Los Angeles, CA 90095, USA.
*   To whom correspondence should be addressed.

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Dual Role of the HIV-1 Vpr Protein in the Modulation of the Apoptotic Response of T Cells.
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M. P. Sherman, C. M. C. de Noronha, D. Pearce, and W. C. Greene (2000)
J. Virol. 74, 8159-8165
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Phosphorylation of Human Immunodeficiency Virus Type 1 Vpr Regulates Cell Cycle Arrest.
Y. Zhou and L. Ratner (2000)
J. Virol. 74, 6520-6527
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HIV-1 envelope induces activation of caspase-3 and cleavage of focal adhesion kinase in primary human CD4+ T cells.
C. Cicala, J. Arthos, A. Rubbert, S. Selig, K. Wildt, O. J. Cohen, and A. S. Fauci (2000)
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A Conserved Dileucine-Containing Motif in p6gag Governs the Particle Association of Vpx and Vpr of Simian Immunodeficiency Viruses SIVmac and SIVagm.
M. A. Accola, A. A. Bukovsky, M. S. Jones, and H. G. Göttlinger (1999)
J. Virol. 73, 9992-9999
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Lentiviral delivery of HIV-1 Vpr protein induces apoptosis in transformed cells.
S. A. Stewart, B. Poon, J. B. M. Jowett, Y. Xie, and I. S. Y. Chen (1999)
PNAS 96, 12039-12043
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The Presence of Human Immunodeficiency Virus Type 1 Vpr Correlates with a Decrease in the Frequency of Mutations in a Plasmid Shuttle Vector.
J. B. Jowett, Y.-m. Xie, and I. S. Y. Chen (1999)
J. Virol. 73, 7132-7137
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Cell Cycle- and Vpr-Mediated Regulation of Human Immunodeficiency Virus Type 1 Expression in Primary and Transformed T-Cell Lines.
S. Gummuluru and M. Emerman (1999)
J. Virol. 73, 5422-5430
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Human Immunodeficiency Virus Type 1 (HIV-1) Vpr Functions as an Immediate-Early Protein during HIV-1 Infection.
M. Hrimech, X.-J. Yao, F. Bachand, N. Rougeau, and E. A. Cohen (1999)
J. Virol. 73, 4101-4109
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Lentivirus Vectors Using Human and Simian Immunodeficiency Virus Elements.
S. M. White, M. Renda, N.-Y. Nam, E. Klimatcheva, Y. Zhu, J. Fisk, M. Halterman, B. J. Rimel, H. Federoff, S. Pandya, et al. (1999)
J. Virol. 73, 2832-2840
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Interaction with the p6 Domain of the Gag Precursor Mediates Incorporation into Virions of Vpr and Vpx Proteins from Primate Lentiviruses.
L. Selig, J.-C. Pages, V. Tanchou, S. Preveral, C. Berlioz-Torrent, L. X. Liu, L. Erdtmann, J.-L. Darlix, R. Benarous, and S. Benichou (1999)
J. Virol. 73, 592-600
   Abstract »    Full Text »    PDF »
Functional and Structural Characterization of Synthetic HIV-1 Vpr That Transduces Cells, Localizes to the Nucleus, and Induces G2 Cell Cycle Arrest.
P. Henklein, K. Bruns, M. P. Sherman, U. Tessmer, K. Licha, J. Kopp, C. M. C. de Noronha, W. C. Greene, V. Wray, and U. Schubert (2000)
J. Biol. Chem. 275, 32016-32026
   Abstract »    Full Text »    PDF »


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