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 Bartz, S. R.
Right arrow Articles by Emerman, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bartz, S. R.
Right arrow Articles by Emerman, M.

 Previous Article  |  Next Article 

Journal of Virology, March 1999, p. 1956-1963, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Human Immunodeficiency Virus Type 1 Tat Induces Apoptosis and Increases Sensitivity to Apoptotic Signals by Up-Regulating FLICE/Caspase-8

Steven R. Bartz and Michael Emerman*

Divisions of Molecular Medicine and Basic Science, Fred Hutchinson Cancer Research Center, Seattle, Washington

Received 22 September 1998/Accepted 20 November 1998

Apoptosis contributes to the loss of CD4 cells during human immunodeficiency virus type 1 (HIV-1) infection. Although the product of the env gene, gp160/gp120, is known to play a role in cell death mediated by HIV-1, the role of other HIV-1 genes in the process is unclear. We found that HIV-1 lacking the env gene (HIVDelta env) still induced apoptosis in T-cell lines and primary CD4 T cells. The ability to induce apoptosis was attributable to Tat, a viral regulatory protein. Tat induction of apoptosis was separate from the transactivation function of Tat, required expression of the second exon of Tat, and was associated with the increased expression and activity of caspase-8 (casp-8), a signaling molecule in apoptotic pathways. Moreover, induction of apoptosis could be prevented by treating cells with an inhibitor of casp-8. In addition, we show that HIV-1Delta env infection and Tat expression increased the sensitivity of cells to Fas-mediated apoptosis, an apoptotic pathway that signals via casp-8. The up-regulation of casp-8 by HIV-1 Tat expression may contribute to the increased apoptosis and sensitivity to apoptotic signals observed in the cells of HIV-1-infected persons.

* Corresponding author. Mailing address: Divisions of Molecular Medicine and Basic Science, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., C2-023, P.O. Box 19024, Seattle, WA 98109-1024. Phone: (206) 667-5058. Fax: (206) 667-6523. E-mail: memerman{at}fhcrc.org.

Journal of Virology, March 1999, p. 1956-1963, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Chan, E. Y., Sutton, J. N., Jacobs, J. M., Bondarenko, A., Smith, R. D., Katze, M. G. (2009). Dynamic Host Energetics and Cytoskeletal Proteomes in Human Immunodeficiency Virus Type 1-Infected Human Primary CD4 Cells: Analysis by Multiplexed Label-Free Mass Spectrometry. J. Virol. 83: 9283-9295 [Abstract] [Full Text]  
  • Gutierrez-Sanmartin, D., Varela-Ledo, E., Aguilera, A., Romero-Yuste, S., Romero-Jung, P., Gomez-Tato, A., Regueiro, B. J. (2008). Implication of p38 mitogen-activated protein kinase isoforms ({alpha}, {beta}, {gamma} and {delta}) in CD4+ T-cell infection with human immunodeficiency virus type I. J. Gen. Virol. 89: 1661-1671 [Abstract] [Full Text]  
  • Mahlknecht, U., Dichamp, I., Varin, A., Van Lint, C., Herbein, G. (2008). NF-{kappa}B-dependent control of HIV-1 transcription by the second coding exon of Tat in T cells. J. Leukoc. Biol. 83: 718-727 [Abstract] [Full Text]  
  • Pingle, S. C., Jajoo, S., Mukherjea, D., Sniderhan, L. F., Jhaveri, K. A., Marcuzzi, A., Rybak, L. P., Maggirwar, S. B., Ramkumar, V. (2007). Activation of the Adenosine A1 Receptor Inhibits HIV-1 Tat-Induced Apoptosis by Reducing Nuclear Factor-{kappa}B Activation and Inducible Nitric-Oxide Synthase. Mol. Pharmacol. 72: 856-867 [Abstract] [Full Text]  
  • O'Hara, S. P., Small, A. J., Nelson, J. B., Badley, A. D., Chen, X.-M., Gores, G. J., LaRusso, N. F. (2007). The Human Immunodeficiency Virus Type 1 Tat Protein Enhances Cryptosporidium parvum-Induced Apoptosis in Cholangiocytes via a Fas Ligand-Dependent Mechanism. Infect. Immun. 75: 684-696 [Abstract] [Full Text]  
  • Madani, N., Hubicki, A. M., Perdigoto, A. L., Springer, M., Sodroski, J. (2007). Inhibition of Human Immunodeficiency Virus Envelope Glycoprotein- Mediated Single Cell Lysis by Low-Molecular-Weight Antagonists of Viral Entry. J. Virol. 81: 532-538 [Abstract] [Full Text]  
  • Zhang, M., Drenkow, J., Lankford, C. S. R., Frucht, D. M., Rabin, R. L., Gingeras, T. R., Venkateshan, C., Schwartzkopff, F., Clouse, K. A., Dayton, A. I. (2006). HIV regulation of the IL-7R: a viral mechanism for enhancing HIV-1 replication in human macrophages in vitro. J. Leukoc. Biol. 79: 1328-1338 [Abstract] [Full Text]  
  • Iannello, A., Debbeche, O., Martin, E., Attalah, L. H., Samarani, S., Ahmad, A. (2006). Viral strategies for evading antiviral cellular immune responses of the host. J. Leukoc. Biol. 79: 16-35 [Abstract] [Full Text]  
  • Montano, M., Rarick, M., Sebastiani, P., Brinkmann, P., Skefos, J., Ericksen, R. (2006). HIV-1 burden influences host response to co-infection with Neisseria gonorrhoeae in vitro. Int Immunol 18: 125-137 [Abstract] [Full Text]  
  • Campbell, G. R., Watkins, J. D., Esquieu, D., Pasquier, E., Loret, E. P., Spector, S. A. (2005). The C Terminus of HIV-1 Tat Modulates the Extent of CD178-mediated Apoptosis of T Cells. J. Biol. Chem. 280: 38376-38382 [Abstract] [Full Text]  
  • Arp, J., Rieder, M. J., Urquhart, B., Freeman, D., Tucker, M. J., Krizova, A., Lehmann, D., Dekaban, G. A. (2005). Hypersensitivity of HIV-1-Infected Cells to Reactive Sulfonamide Metabolites Correlated to Expression of the HIV-1 Viral Protein Tat. J. Pharmacol. Exp. Ther. 314: 1218-1225 [Abstract] [Full Text]  
  • Wiegand, M., Bossow, S., Neubert, W. J. (2005). Sendai virus trailer RNA simultaneously blocks two apoptosis-inducing mechanisms in a cell type-dependent manner. J. Gen. Virol. 86: 2305-2314 [Abstract] [Full Text]  
  • Billotey, C., Aspord, C., Beuf, O., Piaggio, E., Gazeau, F., Janier, M. F., Thivolet, C. (2005). T-Cell Homing to the Pancreas in Autoimmune Mouse Models of Diabetes: In Vivo MR Imaging. Radiology 236: 579-587 [Abstract] [Full Text]  
  • Acheampong, E. A., Parveen, Z., Muthoga, L. W., Wasmuth-Peroud, V., Kalayeh, M., Bashir, A., Diecidue, R., Mukhtar, M., Pomerantz, R. J. (2005). Molecular Interactions of Human Immunodeficiency Virus Type 1 with Primary Human Oral Keratinocytes. J. Virol. 79: 8440-8453 [Abstract] [Full Text]  
  • Walker, F., Adle-Biassette, H., Madelenat, P., Henin, D., Lehy, T. (2005). Increased Apoptosis in Cervical Intraepithelial Neoplasia Associated with HIV Infection: Implication of Oncogenic Human Papillomavirus, Caspases, and Langerhans Cells. Clin. Cancer Res. 11: 2451-2458 [Abstract] [Full Text]  
  • Campbell, G. R., Pasquier, E., Watkins, J., Bourgarel-Rey, V., Peyrot, V., Esquieu, D., Barbier, P., de Mareuil, J., Braguer, D., Kaleebu, P., Yirrell, D. L., Loret, E. P. (2004). The Glutamine-rich Region of the HIV-1 Tat Protein Is Involved in T-cell Apoptosis. J. Biol. Chem. 279: 48197-48204 [Abstract] [Full Text]  
  • Coberley, C. R., Kohler, J. J., Brown, J. N., Oshier, J. T., Baker, H. V., Popp, M. P., Sleasman, J. W., Goodenow, M. M. (2004). Impact on Genetic Networks in Human Macrophages by a CCR5 Strain of Human Immunodeficiency Virus Type 1. J. Virol. 78: 11477-11486 [Abstract] [Full Text]  
  • Moreau, E., Belliard, G., Partidos, C. D., Pradezinsky, F., Le Buanec, H., Muller, S., Desgranges, C. (2004). Important B-cell epitopes for neutralization of human immunodeficiency virus type 1 Tat in serum samples of humans and different animal species immunized with Tat protein or peptides. J. Gen. Virol. 85: 2893-2901 [Abstract] [Full Text]  
  • Yamashita, M., Emerman, M. (2004). Capsid Is a Dominant Determinant of Retrovirus Infectivity in Nondividing Cells. J. Virol. 78: 5670-5678 [Abstract] [Full Text]  
  • Hood, C., Cunningham, A. L., Slobedman, B., Boadle, R. A., Abendroth, A. (2003). Varicella-Zoster Virus-Infected Human Sensory Neurons Are Resistant to Apoptosis, yet Human Foreskin Fibroblasts Are Susceptible: Evidence for a Cell-Type-Specific Apoptotic Response. J. Virol. 77: 12852-12864 [Abstract] [Full Text]  
  • Komoto, S., Tsuji, S., Ibrahim, M. S., Li, Y.-G., Warachit, J., Taniguchi, K., Ikuta, K. (2003). The Vpu Protein of Human Immunodeficiency Virus Type 1 Plays a Protective Role against Virus-Induced Apoptosis in Primary CD4+ T Lymphocytes. J. Virol. 77: 10304-10313 [Abstract] [Full Text]  
  • Alimonti, J. B., Ball, T. B., Fowke, K. R. (2003). Mechanisms of CD4+ T lymphocyte cell death in human immunodeficiency virus infection and AIDS. J. Gen. Virol. 84: 1649-1661 [Abstract] [Full Text]  
  • LaBonte, J. A., Madani, N., Sodroski, J. (2003). Cytolysis by CCR5-Using Human Immunodeficiency Virus Type 1 Envelope Glycoproteins Is Dependent on Membrane Fusion and Can Be Inhibited by High Levels of CD4 Expression. J. Virol. 77: 6645-6659 [Abstract] [Full Text]  
  • Yang, Y., Tikhonov, I., Ruckwardt, T. J., Djavani, M., Zapata, J. C., Pauza, C. D., Salvato, M. S. (2003). Monocytes Treated with Human Immunodeficiency Virus Tat Kill Uninfected CD4+ Cells by a Tumor Necrosis Factor-Related Apoptosis-Induced Ligand-Mediated Mechanism. J. Virol. 77: 6700-6708 [Abstract] [Full Text]  
  • Tikhonov, I., Ruckwardt, T. J., Hatfield, G. S., Pauza, C. D. (2003). Tat-Neutralizing Antibodies in Vaccinated Macaques. J. Virol. 77: 3157-3166 [Abstract] [Full Text]  
  • Bitzer, M., Armeanu, S., Prinz, F., Ungerechts, G., Wybranietz, W., Spiegel, M., Bernlohr, C., Cecconi, F., Gregor, M., Neubert, W. J., Schulze-Osthoff, K., Lauer, U. M. (2002). Caspase-8 and Apaf-1-independent Caspase-9 Activation in Sendai Virus-infected Cells. J. Biol. Chem. 277: 29817-29824 [Abstract] [Full Text]  
  • Labrada, L., Bodelon, G., Vinuela, J., Benavente, J. (2002). Avian Reoviruses Cause Apoptosis in Cultured Cells: Viral Uncoating, but Not Viral Gene Expression, Is Required for Apoptosis Induction. J. Virol. 76: 7932-7941 [Abstract] [Full Text]  
  • Li, J., Liu, Y., Kim, B. O., He, J. J. (2002). Direct Participation of Sam68, the 68-Kilodalton Src-Associated Protein in Mitosis, in the CRM1-Mediated Rev Nuclear Export Pathway. J. Virol. 76: 8374-8382 [Abstract] [Full Text]  
  • Hay, S., Kannourakis, G. (2002). A time to kill: viral manipulation of the cell death program. J. Gen. Virol. 83: 1547-1564 [Abstract] [Full Text]  
  • Yang, Y., Dong, B., Mittelstadt, P. R., Xiao, H., Ashwell, J. D. (2002). HIV Tat Binds Egr Proteins and Enhances Egr-dependent Transactivation of the Fas Ligand Promoter. J. Biol. Chem. 277: 19482-19487 [Abstract] [Full Text]  
  • Garden, G. A., Budd, S. L., Tsai, E., Hanson, L., Kaul, M., D'Emilia, D. M., Friedlander, R. M., Yuan, J., Masliah, E., Lipton, S. A. (2002). Caspase Cascades in Human Immunodeficiency Virus-Associated Neurodegeneration. J. Neurosci. 22: 4015-4024 [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]  
  • Bolton, D. L., Hahn, B.-I., Park, E. A., Lehnhoff, L. L., Hornung, F., Lenardo, M. J. (2002). Death of CD4+ T-Cell Lines Caused by Human Immunodeficiency Virus Type 1 Does Not Depend on Caspases or Apoptosis. J. Virol. 76: 5094-5107 [Abstract] [Full Text]  
  • de Oliveira Pinto, L. M., Garcia, S., Lecoeur, H., Rapp, C., Gougeon, M.-L. (2002). Increased sensitivity of T lymphocytes to tumor necrosis factor receptor 1 (TNFR1)- and TNFR2-mediated apoptosis in HIV infection: relation to expression of Bcl-2 and active caspase-8 and caspase-3. Blood 99: 1666-1675 [Abstract] [Full Text]  
  • Gjoerup, O., Zaveri, D., Roberts, T. M. (2001). Induction of p53-Independent Apoptosis by Simian Virus 40 Small t Antigen. J. Virol. 75: 9142-9155 [Abstract] [Full Text]  
  • Morita-Fujimura, Y., Fujimura, M., Yoshimoto, T., Chan, P. H. (2001). Superoxide During Reperfusion Contributes to Caspase-8 Expression and Apoptosis After Transient Focal Stroke. Stroke 32: 2356-2361 [Abstract] [Full Text]  
  • Yoshimura, F. K., Wang, T., Nanua, S. (2001). Mink Cell Focus-Forming Murine Leukemia Virus Killing of Mink Cells Involves Apoptosis and Superinfection. J. Virol. 75: 6007-6015 [Abstract] [Full Text]  
  • Etemad-Moghadam, B., Rhone, D., Steenbeke, T., Sun, Y., Manola, J., Gelman, R., Fanton, J. W., Racz, P., Tenner-Racz, K., Axthelm, M. K., Letvin, N. L., Sodroski, J. (2001). Membrane-Fusing Capacity of the Human Immunodeficiency Virus Envelope Proteins Determines the Efficiency of CD4+ T-Cell Depletion in Macaques Infected by a Simian-Human Immunodeficiency Virus. J. Virol. 75: 5646-5655 [Abstract] [Full Text]  
  • Gonzalez, E., Punzon, C., Gonzalez, M., Fresno, M. (2001). HIV-1 Tat Inhibits IL-2 Gene Transcription Through Qualitative and Quantitative Alterations of the Cooperative Rel/AP1 Complex Bound to the CD28RE/AP1 Composite Element of the IL-2 Promoter. J. Immunol. 166: 4560-4569 [Abstract] [Full Text]  
  • LaBonte, J. A., Patel, T., Hofmann, W., Sodroski, J. (2000). Importance of Membrane Fusion Mediated by Human Immunodeficiency Virus Envelope Glycoproteins for Lysis of Primary CD4-Positive T Cells. J. Virol. 74: 10690-10698 [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]  
  • Nishizawa, M., Kamata, M., Katsumata, R., Aida, Y. (2000). A Carboxy-Terminally Truncated Form of the Human Immunodeficiency Virus Type 1 Vpr Protein Induces Apoptosis via G1 Cell Cycle Arrest. J. Virol. 74: 6058-6067 [Abstract] [Full Text]  
  • Cicala, C., Arthos, J., Rubbert, A., Selig, S., Wildt, K., Cohen, O. J., Fauci, A. S. (2000). HIV-1 envelope induces activation of caspase-3 and cleavage of focal adhesion kinase in primary human CD4+ T cells. Proc. Natl. Acad. Sci. USA 97: 1178-1183 [Abstract] [Full Text]  
  • Micoli, K. J., Pan, G., Wu, Y., Williams, J. P., Cook, W. J., McDonald, J. M. (2000). Requirement of Calmodulin Binding by HIV-1 gp160 for Enhanced FAS-mediated Apoptosis. J. Biol. Chem. 275: 1233-1240 [Abstract] [Full Text]  
  • Pauza, C. D., Trivedi, P., Wallace, M., Ruckwardt, T. J., Le Buanec, H., Lu, W., Bizzini, B., Burny, A., Zagury, D., Gallo, R. C. (2000). Vaccination with Tat toxoid attenuates disease in simian/HIV-challenged macaques. Proc. Natl. Acad. Sci. USA 97: 3515-3519 [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»