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 Ndolo, T.
Right arrow Articles by Dandekar, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ndolo, T.
Right arrow Articles by Dandekar, S.

Next Article 

Journal of Virology, April 2002, p. 3587-3595, Vol. 76, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.8.3587-3595.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Simian Immunodeficiency Virus Nef Protein Delays the Progression of CD4+ T Cells through G1/S Phase of the Cell Cycle

Thomas Ndolo,1 Navdeep K. Dhillon,2 Hau Nguyen,1 Moraima Guadalupe,1 Maria Mudryj,2 and Satya Dandekar1*

Departments of Internal Medicine,1 Medical Microbiology, School of Medicine, University of California, Davis, California 956162

Received 5 September 2001/ Accepted 9 January 2002

Human and simian immunodeficiency virus (HIV and SIV, respectively) infections are characterized by gradual depletion of CD4+ T cells. The underlying mechanisms of CD4+ T-cell depletion and HIV and SIV persistence are not fully determined. The Nef protein is expressed early in infection and is necessary for pathogenesis. Nef can cause T-cell activation and downmodulates cell surface signaling molecules. However, the effect of Nef on the cell cycle has not been well characterized. To determine the role of Nef in the cell cycle, we investigated whether the SIV Nef protein can modulate cell proliferation and apoptosis in CD4+ Jurkat T cells. We developed a CD4+ Jurkat T-cell line that stably expresses SIV Nef under the control of an inducible promoter. Alterations in cell proliferation were determined by flow cytometry using stable intracytoplasmic fluorescent dye 5- and 6-carboxyfluorescein diacetate succinimidyl ester and bromodeoxyuridine incorporation. Apoptotic cell death was measured by annexin V and propidium iodide staining. Our results demonstrated that SIV Nef inhibited Fas-induced apoptosis in these cells and that the mechanism involved upregulation of the Bcl-2 protein. SIV Nef suppressed CD4+ T-cell proliferation by inhibiting the progression of cells into S phase of the cell cycle. Suppression involved an upregulation of cyclin-dependent kinase inhibitors p21 and p27 and the downregulation of cyclin D1 and cyclin A. In summary, inhibition of apoptosis by Nef can lead to persistence of infected cells and can support viral replication. In addition, a Nef-mediated delay in cell cycle progression may contribute to CD4+ T-cell anergy/depletion seen in HIV and SIV disease.

* Corresponding author. Mailing address: Division of Infectious and Immunologic Diseases, School of Medicine, University of California-Davis, Davis, CA 95616. Phone: (530) 752-3409. Fax (530) 752-8692. E-mail: sdandekar{at}ucdavis.edu.

Journal of Virology, April 2002, p. 3587-3595, Vol. 76, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.8.3587-3595.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lewandowski, D., Marquis, M., Aumont, F., Lussier-Morin, A.-C., Raymond, M., Senechal, S., Hanna, Z., Jolicoeur, P., de Repentigny, L. (2006). Altered CD4+ T Cell Phenotype and Function Determine the Susceptibility to Mucosal Candidiasis in Transgenic Mice Expressing HIV-1. J. Immunol. 177: 479-491 [Abstract] [Full Text]  
  • Bahbouhi, B., Landay, A., Al-Harthi, L. (2004). Dynamics of cytokine expression in HIV productively infected primary CD4+ T cells. Blood 103: 4581-4587 [Abstract] [Full Text]  
  • Weng, X., Priceputu, E., Chrobak, P., Poudrier, J., Kay, D. G., Hanna, Z., Mak, T. W., Jolicoeur, P. (2004). CD4+ T Cells from CD4C/HIVNef Transgenic Mice Show Enhanced Activation In Vivo with Impaired Proliferation In Vitro but Are Dispensable for the Development of a Severe AIDS-Like Organ Disease. J. Virol. 78: 5244-5257 [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»