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 Lenardo, M. J.
Right arrow Articles by Bolton, D. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lenardo, M. J.
Right arrow Articles by Bolton, D. L.

 Previous Article  |  Next Article 

Journal of Virology, May 2002, p. 5082-5093, Vol. 76, No. 10
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.10.5082-5093.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Cytopathic Killing of Peripheral Blood CD4+ T Lymphocytes by Human Immunodeficiency Virus Type 1 Appears Necrotic rather than Apoptotic and Does Not Require env

Michael J. Lenardo,1* Sara B. Angleman,1 Viengngeun Bounkeua,1 Joseph Dimas,1,{dagger} Melody G. Duvall,1,{ddagger} Moses B. Graubard,1 Felicita Hornung,1,§ Marianne C. Selkirk,1,|| Christina K. Speirs,1 Carol Trageser,1 Jan O. Orenstein,2 and Diane L. Bolton1

Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892,1 Department of Pathology, George Washington University, Washington, D.C. 200522

Received 30 October 2001/ Accepted 8 February 2002

An important unresolved issue of AIDS pathogenesis is the mechanism of human immunodeficiency virus (HIV)-induced CD4+ T-lymphocyte destruction. We show here that HIV type 1 (HIV-1) exerts a profound cytopathic effect upon peripheral blood CD4+ T lymphocytes that resembles necrosis rather than apoptosis. Necrotic cytopathology was found with both laboratory-adapted strains and primary isolates of HIV-1. We carefully investigated the role of env, which has been previously implicated in HIV cytopathicity. HIV-1 stocks with equivalent infectivity were prepared from constructs with either an intact or mutated env coding region and pseudotyped with the glycoprotein of vesicular stomatitis virus (VSV-G) so that the HIV envelope was not rate-limiting for infection. Infected Jurkat T cells died whether or not env was intact; however, the expression of env accelerated death significantly. The accelerated death was blocked by protease inhibitors, indicating that it was due to reinfection by newly produced virus in env+ cultures. Accordingly, we found no disparity in kinetics in CD4lo Jurkat cells. In highly infected peripheral blood T cells, profound necrosis occurred equivalently with both env+ and env- stocks of HIV-1. We also found that HIV-1 cytopathicity was undiminished by the absence of nef. However, viral stocks made by complementation or packaging of HIV-1 genomes with the natural protein-coding sequences replaced by the green fluorescent protein were highly infectious but not cytopathic. Thus, env can accelerate cell death chiefly as an entry function, but one or more viral functions other than env or nef is essential for necrosis of CD4+ T cells induced by HIV-1.

* Corresponding author. Mailing address: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg. 10, Rm. 11N311, 10 Center Dr., MSC 1892, Bethesda, MD 20892-1892. Phone: (301) 496-6754. Fax: (301) 480-7352. E-mail: Lenardo{at}nih.gov.

{dagger} Present address: The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229.

{ddagger} Present address: Washington University School of Medicine, St. Louis, MO 63110.

§ Present address: Department of Genetics and Microbiology, University of Geneva, Geneva, Switzerland.

|| Present address: Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305.

Journal of Virology, May 2002, p. 5082-5093, Vol. 76, No. 10
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.10.5082-5093.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zhou, Y., Shen, L., Yang, H.-C., Siliciano, R. F. (2008). Preferential Cytolysis of Peripheral Memory CD4+ T Cells by In Vitro X4-Tropic Human Immunodeficiency Virus Type 1 Infection before the Completion of Reverse Transcription. J. Virol. 82: 9154-9163 [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]  
  • Laforge, M., Petit, F., Estaquier, J., Senik, A. (2007). Commitment to Apoptosis in CD4+ T Lymphocytes Productively Infected with Human Immunodeficiency Virus Type 1 Is Initiated by Lysosomal Membrane Permeabilization, Itself Induced by the Isolated Expression of the Viral Protein Nef. J. Virol. 81: 11426-11440 [Abstract] [Full Text]  
  • Bolton, D. L., Lenardo, M. J. (2007). Vpr Cytopathicity Independent of G2/M Cell Cycle Arrest in Human Immunodeficiency Virus Type 1-Infected CD4+ T Cells. J. Virol. 81: 8878-8890 [Abstract] [Full Text]  
  • Schacker, T. W., Brenchley, J. M., Beilman, G. J., Reilly, C., Pambuccian, S. E., Taylor, J., Skarda, D., Larson, M., Douek, D. C., Haase, A. T. (2006). Lymphatic Tissue Fibrosis Is Associated with Reduced Numbers of Naive CD4+ T Cells in Human Immunodeficiency Virus Type 1 Infection.. CVI 13: 556-560 [Abstract] [Full Text]  
  • Sakai, K., Dimas, J., Lenardo, M. J. (2006). The Vif and Vpr accessory proteins independently cause HIV-1-induced T cell cytopathicity and cell cycle arrest. Proc. Natl. Acad. Sci. USA 103: 3369-3374 [Abstract] [Full Text]  
  • Zong, W.-X., Thompson, C. B. (2006). Necrotic death as a cell fate.. Genes Dev. 20: 1-15 [Abstract] [Full Text]  
  • Holm, G. H., Gabuzda, D. (2005). Distinct Mechanisms of CD4+ and CD8+ T-Cell Activation and Bystander Apoptosis Induced by Human Immunodeficiency Virus Type 1 Virions. J. Virol. 79: 6299-6311 [Abstract] [Full Text]  
  • Priceputu, E., Rodrigue, I., Chrobak, P., Poudrier, J., Mak, T. W., Hanna, Z., Hu, C., Kay, D. G., Jolicoeur, P. (2005). The Nef-Mediated AIDS-Like Disease of CD4C/Human Immunodeficiency Virus Transgenic Mice Is Associated with Increased Fas/FasL Expression on T Cells and T-Cell Death but Is Not Prevented in Fas-, FasL-, Tumor Necrosis Factor Receptor 1-, or Interleukin-1{beta}-Converting Enzyme-Deficient or Bcl2-Expressing Transgenic Mice. J. Virol. 79: 6377-6391 [Abstract] [Full Text]  
  • Speirs, C., van Nimwegen, E., Bolton, D., Zavolan, M., Duvall, M., Angleman, S., Siegel, R., Perelson, A. S., Lenardo, M. J. (2005). Analysis of Human Immunodeficiency Virus Cytopathicity by Using a New Method for Quantitating Viral Dynamics in Cell Culture. J. Virol. 79: 4025-4032 [Abstract] [Full Text]  
  • Alroy, I., Tuvia, S., Greener, T., Gordon, D., Barr, H. M., Taglicht, D., Mandil-Levin, R., Ben-Avraham, D., Konforty, D., Nir, A., Levius, O., Bicoviski, V., Dori, M., Cohen, S., Yaar, L., Erez, O., Propheta-Meiran, O., Koskas, M., Caspi-Bachar, E., Alchanati, I., Sela-Brown, A., Moskowitz, H., Tessmer, U., Schubert, U., Reiss, Y. (2005). The trans-Golgi network-associated human ubiquitin-protein ligase POSH is essential for HIV type 1 production. Proc. Natl. Acad. Sci. USA 102: 1478-1483 [Abstract] [Full Text]  
  • Blanco, J., Barretina, J., Clotet, B., Este, J. A. (2004). R5 HIV gp120-mediated cellular contacts induce the death of single CCR5-expressing CD4 T cells by a gp41-dependent mechanism. J. Leukoc. Biol. 76: 804-811 [Abstract] [Full Text]  
  • Holm, G. H., Zhang, C., Gorry, P. R., Peden, K., Schols, D., De Clercq, E., Gabuzda, D. (2004). Apoptosis of Bystander T Cells Induced by Human Immunodeficiency Virus Type 1 with Increased Envelope/Receptor Affinity and Coreceptor Binding Site Exposure. J. Virol. 78: 4541-4551 [Abstract] [Full Text]  
  • Stebbing, J., Gazzard, B., Douek, D. C. (2004). Where Does HIV Live?. NEJM 350: 1872-1880 [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]  
  • 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]  


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