This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hrimech, M.
Right arrow Articles by Cohen, E. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hrimech, M.
Right arrow Articles by Cohen, E. A.

 Previous Article  |  Next Article 

Journal of Virology, May 1999, p. 4101-4109, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Human Immunodeficiency Virus Type 1 (HIV-1) Vpr Functions as an Immediate-Early Protein during HIV-1 Infection

Mohammed Hrimech, Xiao-Jian Yao, François Bachand, Nicole Rougeau, and Éric A. Cohen*

Laboratoire de Rétrovirologie Humaine, Département de Microbiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada H3C 3J7

Received 30 October 1998/Accepted 29 January 1999

Human immunodeficiency virus type 1 (HIV-1) Vpr is a virion-associated protein which facilitates HIV-1 infection of nondividing cells by contributing to the nuclear transport of the preintegration complex (PIC). Vpr was also shown to induce a cell cycle G2 arrest in infected proliferating cells that optimizes HIV-1 long terminal repeat (LTR)-directed gene expression and viral production. However, it is unclear whether this activity is mediated primarily early by virion-associated Vpr or alternatively late during infection when Vpr is de novo expressed. We report here that in the absence of de novo expression, virion-associated Vpr induces a transient G2 arrest that can subsequently lead to cell killing by apoptosis. Interestingly, the induction of both cell cycle G2 arrest and apoptosis by virion-associated Vpr requires viral entry but not viral replication, since reverse transcriptase and protease inhibitor treatments do not prevent these Vpr effects. These results raise the possibility that in vivo both infectious and noninfectious viruses contribute to the dysfunction and killing of CD4+ cells. In addition, our results reveal that virion-associated Vpr stimulates viral replication in proliferating cells after establishing a cell cycle G2 arrest by increasing LTR-directed gene expression. Importantly, this Vpr-mediated LTR activation appears to be a requirement for subsequent optimal Tat transactivation. Taken together, these results strongly suggest that in addition to participating in the HIV PIC nuclear transport in nondividing cells, virion-associated Vpr activates HIV-1 LTR-directed gene expression by manipulating the host cell cycle. From this, we conclude that Vpr functions as an immediate-early protein during HIV-1 infection.

* Corresponding author. Mailing address: Laboratoire de Rétrovirologie Humaine, Département de Microbiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada H3C 3J7. Phone: (514) 343-5967. Fax: (514) 343-5995. E-mail: eric.cohen{at}umontreal.ca.

Journal of Virology, May 1999, p. 4101-4109, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Poon, B., Chang, M. A., Chen, I. S. Y. (2007). Vpr Is Required for Efficient Nef Expression from Unintegrated Human Immunodeficiency Virus Type 1 DNA. J. Virol. 81: 10515-10523 [Abstract] [Full Text]  
  • Zimmerman, E. S., Sherman, M. P., Blackett, J. L., Neidleman, J. A., Kreis, C., Mundt, P., Williams, S. A., Warmerdam, M., Kahn, J., Hecht, F. M., Grant, R. M., de Noronha, C. M. C., Weyrich, A. S., Greene, W. C., Planelles, V. (2006). Human Immunodeficiency Virus Type 1 Vpr Induces DNA Replication Stress In Vitro and In Vivo. J. Virol. 80: 10407-10418 [Abstract] [Full Text]  
  • Yedavalli, V. S. R. K., Shih, H.-M., Chiang, Y.-P., Lu, C.-Y., Chang, L.-Y., Chen, M.-Y., Chuang, C.-Y., Dayton, A. I., Jeang, K.-T., Huang, L.-M. (2005). Human Immunodeficiency Virus Type 1 Vpr Interacts with Antiapoptotic Mitochondrial Protein HAX-1. J. Virol. 79: 13735-13746 [Abstract] [Full Text]  
  • Yoshizuka, N., Yoshizuka-Chadani, Y., Krishnan, V., Zeichner, S. L. (2005). Human Immunodeficiency Virus Type 1 Vpr-Dependent Cell Cycle Arrest through a Mitogen-Activated Protein Kinase Signal Transduction Pathway. J. Virol. 79: 11366-11381 [Abstract] [Full Text]  
  • DeHart, J. L., Andersen, J. L., Zimmerman, E. S., Ardon, O., An, D. S., Blackett, J., Kim, B., Planelles, V. (2005). The Ataxia Telangiectasia-Mutated and Rad3-Related Protein Is Dispensable for Retroviral Integration. J. Virol. 79: 1389-1396 [Abstract] [Full Text]  
  • Kino, T., De Martino, M. U., Charmandari, E., Ichijo, T., Outas, T., Chrousos, G. P. (2005). HIV-1 Accessory Protein Vpr Inhibits the Effect of Insulin on the Foxo Subfamily of Forkhead Transcription Factors by Interfering With Their Binding to 14-3-3 Proteins: Potential Clinical Implications Regarding the Insulin Resistance of HIV-1-Infected Patients. Diabetes 54: 23-31 [Abstract] [Full Text]  
  • Beriault, V., Clement, J.-F., Levesque, K., LeBel, C., Yong, X., Chabot, B., Cohen, E. A., Cochrane, A. W., Rigby, W. F. C., Mouland, A. J. (2004). A Late Role for the Association of hnRNP A2 with the HIV-1 hnRNP A2 Response Elements in Genomic RNA, Gag, and Vpr Localization. J. Biol. Chem. 279: 44141-44153 [Abstract] [Full Text]  
  • Cocude, C., Truong, M.-J., Billaut-Mulot, O., Delsart, V., Darcissac, E., Capron, A., Mouton, Y., Bahr, G. M. (2003). A novel cellular RNA helicase, RH116, differentially regulates cell growth, programmed cell death and human immunodeficiency virus type 1 replication. J. Gen. Virol. 84: 3215-3225 [Abstract] [Full Text]  
  • Rohr, O., Marban, C., Aunis, D., Schaeffer, E. (2003). Regulation of HIV-1 gene transcription: from lymphocytes to microglial cells. J. Leukoc. Biol. 74: 736-749 [Abstract] [Full Text]  
  • Bruns, K., Fossen, T., Wray, V., Henklein, P., Tessmer, U., Schubert, U. (2003). Structural Characterization of the HIV-1 Vpr N Terminus: EVIDENCE OF cis/trans-PROLINE ISOMERISM. J. Biol. Chem. 278: 43188-43201 [Abstract] [Full Text]  
  • Roshal, M., Kim, B., Zhu, Y., Nghiem, P., Planelles, V. (2003). Activation of the ATR-mediated DNA Damage Response by the HIV-1 Viral Protein R. J. Biol. Chem. 278: 25879-25886 [Abstract] [Full Text]  
  • Sherman, M. P., de Noronha, C. M. C., Eckstein, L. A., Hataye, J., Mundt, P., Williams, S. A. F., Neidleman, J. A., Goldsmith, M. A., Greene, W. C. (2003). Nuclear Export of Vpr Is Required for Efficient Replication of Human Immunodeficiency Virus Type 1 in Tissue Macrophages. J. Virol. 77: 7582-7589 [Abstract] [Full Text]  
  • Poon, B., Chen, I. S. Y. (2003). Human Immunodeficiency Virus Type 1 (HIV-1) Vpr Enhances Expression from Unintegrated HIV-1 DNA. J. Virol. 77: 3962-3972 [Abstract] [Full Text]  
  • Yuan, H., Xie, Y.-M., Chen, I. S. Y. (2003). Depletion of Wee-1 Kinase Is Necessary for both Human Immunodeficiency Virus Type 1 Vpr- and Gamma Irradiation-Induced Apoptosis. J. Virol. 77: 2063-2070 [Abstract] [Full Text]  
  • Kino, T., Gragerov, A., Slobodskaya, O., Tsopanomichalou, M., Chrousos, G. P., Pavlakis, G. N. (2002). Human Immunodeficiency Virus Type 1 (HIV-1) Accessory Protein Vpr Induces Transcription of the HIV-1 and Glucocorticoid-Responsive Promoters by Binding Directly to p300/CBP Coactivators. J. Virol. 76: 9724-9734 [Abstract] [Full Text]  
  • Lenardo, M. J., Angleman, S. B., Bounkeua, V., Dimas, J., Duvall, M. G., Graubard, M. B., Hornung, F., Selkirk, M. C., Speirs, C. K., Trageser, C., Orenstein, J. O., Bolton, D. L. (2002). Cytopathic Killing of Peripheral Blood CD4+ T Lymphocytes by Human Immunodeficiency Virus Type 1 Appears Necrotic rather than Apoptotic and Does Not Require env. J. Virol. 76: 5082-5093 [Abstract] [Full Text]  
  • Eckstein, D. A., Sherman, M. P., Penn, M. L., Chin, P. S., De Noronha, C. M.C., Greene, W. C., Goldsmith, M. A. (2001). HIV-1 Vpr Enhances Viral Burden by Facilitating Infection of Tissue Macrophages but Not Nondividing CD4+ T Cells. JEM 194: 1407-1419 [Abstract] [Full Text]  
  • Akari, H., Bour, S., Kao, S., Adachi, A., Strebel, K. (2001). The Human Immunodeficiency Virus Type 1 Accessory Protein Vpu Induces Apoptosis by Suppressing the Nuclear Factor {kappa}B-dependent Expression of Antiapoptotic Factors. JEM 194: 1299-1312 [Abstract] [Full Text]  
  • de Noronha, C. M. C., Sherman, M. P., Lin, H. W., Cavrois, M. V., Moir, R. D., Goldman, R. D., Greene, W. C. (2001). Dynamic Disruptions in Nuclear Envelope Architecture and Integrity Induced by HIV-1 Vpr. Science 294: 1105-1108 [Abstract] [Full Text]  
  • Jenkins, Y., Pornillos, O., Rich, R. L., Myszka, D. G., Sundquist, W. I., Malim, M. H. (2001). Biochemical Analyses of the Interactions between Human Immunodeficiency Virus Type 1 Vpr and p6Gag. J. Virol. 75: 10537-10542 [Abstract] [Full Text]  
  • Sherman, M. P., de Noronha, C. M. C., Heusch, M. I., Greene, S., Greene, W. C. (2001). Nucleocytoplasmic Shuttling by Human Immunodeficiency Virus Type 1 Vpr. J. Virol. 75: 1522-1532 [Abstract] [Full Text]  
  • Conti, L., Varano, B., Gauzzi, M. C., Matarrese, P., Federico, M., Malorni, W., Belardelli, F., Gessani, S. (2000). Impairment of Human Immunodeficiency Virus Type 1 (HIV-1) Entry into Jurkat T Cells by Constitutive Expression of the HIV-1 Vpr Protein: Role of CD4 Down-Modulation. J. Virol. 74: 10207-10211 [Abstract] [Full Text]  
  • Badley, A. D., Pilon, A. A., Landay, A., Lynch, D. H. (2000). Mechanisms of HIV-associated lymphocyte apoptosis. Blood 96: 2951-2964 [Abstract] [Full Text]  
  • Patel, C. A., Mukhtar, M., Pomerantz, R. J. (2000). Human Immunodeficiency Virus Type 1 Vpr Induces Apoptosis in Human Neuronal Cells. J. Virol. 74: 9717-9726 [Abstract] [Full Text]  
  • Conti, L., Matarrese, P., Varano, B., Gauzzi, M. C., Sato, A., Malorni, W., Belardelli, F., Gessani, S. (2000). Dual Role of the HIV-1 Vpr Protein in the Modulation of the Apoptotic Response of T Cells. J. Immunol. 165: 3293-3300 [Abstract] [Full Text]  
  • Sherman, M. P., de Noronha, C. M. C., Pearce, D., Greene, W. C. (2000). Human Immunodeficiency Virus Type 1 Vpr Contains Two Leucine-Rich Helices That Mediate Glucocorticoid Receptor Coactivation Independently of Its Effects on G2 Cell Cycle Arrest. J. Virol. 74: 8159-8165 [Abstract] [Full Text]  
  • Zhou, Y., Ratner, L. (2000). Phosphorylation of Human Immunodeficiency Virus Type 1 Vpr Regulates Cell Cycle Arrest. J. Virol. 74: 6520-6527 [Abstract] [Full Text]  
  • Roux, P., Alfieri, C., Hrimech, M., Cohen, E. A., Tanner, J. E. (2000). Activation of Transcription Factors NF-kappa B and NF-IL-6 by Human Immunodeficiency Virus Type 1 Protein R (Vpr) Induces Interleukin-8 Expression. J. Virol. 74: 4658-4665 [Abstract] [Full Text]  
  • Jacotot, E., Ravagnan, L., Loeffler, M., Ferri, K. F., Vieira, H. L.A., Zamzami, N., Costantini, P., Druillennec, S., Hoebeke, J., Briand, J. P., Irinopoulou, T., Daugas, E., Susin, S. A., Cointe, D., Xie, Z. H., Reed, J. C., Roques, B. P., Kroemer, G. (2000). The HIV-1 Viral Protein R Induces Apoptosis via a Direct Effect on the Mitochondrial Permeability Transition Pore. JEM 191: 33-46 [Abstract] [Full Text]  
  • Henklein, P., Bruns, K., Sherman, M. P., Tessmer, U., Licha, K., Kopp, J., de Noronha, C. M. C., Greene, W. C., Wray, V., Schubert, U. (2000). Functional and Structural Characterization of Synthetic HIV-1 Vpr That Transduces Cells, Localizes to the Nucleus, and Induces G2 Cell Cycle Arrest. J. Biol. Chem. 275: 32016-32026 [Abstract] [Full Text]  
  • Sawaya, B. E., Khalili, K., Gordon, J., Taube, R., Amini, S. (2000). Cooperative Interaction between HIV-1 Regulatory Proteins Tat and Vpr Modulates Transcription of the Viral Genome. J. Biol. Chem. 275: 35209-35214 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»