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

 Previous Article  |  Next Article 

J. Virol., 03 1996, 1340-1354, Vol 70, No. 3
Copyright © 1996, American Society for Microbiology

Molecular determinants of acute single-cell lysis by human immunodeficiency virus type 1

J Cao, IW Park, A Cooper and J Sodroski
Division of Human Retrovirology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Human immunodeficiency virus type 1 (HIV-1) infection of CD4-positive lymphocytes is accompanied by acute cytopathic effects, i.e., syncytium formation and single-cell lysis. Syncytium formation involves cell-cell fusion mediated by viral envelope glycoproteins on the surface of infected cells and by CD4 glycoproteins on adjacent cells. The molecular basis for the lysis of single-HIV-1 infected cells is unclear. Here we report that the expression of functional envelope glycoproteins from primary and laboratory-adapted HIV-1 isolates resulted in the lysis of single CD4-positive lymphocytes. As was previously observed in HIV-1 infected cultures, single-cell lysis in this system primarily involved necrosis and was not inhibited by soluble CD4. Binding of the viral envelope glycoproteins to the CD4 glycoprotein facilitated, but was not sufficient for, cytolysis. Importantly, the ability of the HIV-1 envelope glycoproteins to mediate membrane fusion was essential for single-cell killing. By contrast, the long cytoplasmic tail of the gp41 transmembrane envelope glycoprotein was neither necessary nor sufficient for single-cell lysis. These results suggest that intracellular envelope glycoprotein-CD4 interactions initiate autofusion events that disrupt cell membrane integrity, leading to single-cell lysis by HIV-1.

This article has been cited by other articles:

• 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]  
• Veazey, R. S., Acierno, P. M., McEvers, K. J., Baumeister, S. H. C., Foster, G. J., Rett, M. D., Newberg, M. H., Kuroda, M. J., Williams, K., Kim, E.-Y., Wolinsky, S. M., Rieber, E. P., Piatak, M. Jr., Lifson, J. D., Montefiori, D. C., Brown, C. R., Hirsch, V. M., Schmitz, J. E. (2008). Increased Loss of CCR5+ CD45RA- CD4+ T Cells in CD8+ Lymphocyte-Depleted Simian Immunodeficiency Virus-Infected Rhesus Monkeys. J. Virol. 82: 5618-5630 [Abstract] [Full Text]  
• Huang, I-C., Li, W., Sui, J., Marasco, W., Choe, H., Farzan, M. (2008). Influenza A Virus Neuraminidase Limits Viral Superinfection. J. Virol. 82: 4834-4843 [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]  
• Garg, H., Joshi, A., Freed, E. O., Blumenthal, R. (2007). Site-specific Mutations in HIV-1 gp41 Reveal a Correlation between HIV-1-mediated Bystander Apoptosis and Fusion/Hemifusion. J. Biol. Chem. 282: 16899-16906 [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]  
• 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]  
• Huerta, L., Gomez-Icazbalceta, G., Soto-Ramirez, L., Viveros-Rogel, M., Rodriguez, R., Fuentes, L., Lamoyi, E., Larralde, C. (2005). Human immunodeficiency virus 1 (HIV-1) envelope-dependent cell-cell fusion modulation by HIV-positive sera is related to disease progression. J. Gen. Virol. 86: 1961-1966 [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]  
• 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]  
• Jin, H., Carlile, C., Nolan, S., Grote, E. (2004). Prm1 Prevents Contact-Dependent Lysis of Yeast Mating Pairs. Eukaryot Cell 3: 1664-1673 [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]  
• Wu, Y., Marsh, J. W. (2003). Early Transcription from Nonintegrated DNA in Human Immunodeficiency Virus Infection. J. Virol. 77: 10376-10382 [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]  
• Kalia, V., Sarkar, S., Gupta, P., Montelaro, R. C. (2003). Rational Site-Directed Mutations of the LLP-1 and LLP-2 Lentivirus Lytic Peptide Domains in the Intracytoplasmic Tail of Human Immunodeficiency Virus Type 1 gp41 Indicate Common Functions in Cell-Cell Fusion but Distinct Roles in Virion Envelope Incorporation. J. Virol. 77: 3634-3646 [Abstract] [Full Text]  
• Blanco, R., Carrasco, L., Ventoso, I. (2003). Cell Killing by HIV-1 Protease. J. Biol. Chem. 278: 1086-1093 [Abstract] [Full Text]  
• Somasundaran, M., Sharkey, M., Brichacek, B., Luzuriaga, K., Emerman, M., Sullivan, J. L., Stevenson, M. (2002). Evidence for a cytopathogenicity determinant in HIV-1 Vpr. Proc. Natl. Acad. Sci. USA 99: 9503-9508 [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]  
• 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]  
• Barsov, E. V., Payne, W. S., Hughes, S. H. (2001). Adaptation of Chimeric Retroviruses In Vitro and In Vivo: Isolation of Avian Retroviral Vectors with Extended Host Range. J. Virol. 75: 4973-4983 [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]  
• Stocker, H., Scheller, C., Jassoy, C. (2000). Destruction of primary CD4+ T cells by cell-cell interaction in human immunodeficiency virus type 1 infection in vitro. J. Gen. Virol. 81: 1907-1911 [Abstract] [Full Text]  
• Etemad-Moghadam, B., Sun, Y., Nicholson, E. K., Fernandes, M., Liou, K., Gomila, R., Lee, J., Sodroski, J. (2000). Envelope Glycoprotein Determinants of Increased Fusogenicity in a Pathogenic Simian-Human Immunodeficiency Virus (SHIV-KB9) Passaged In Vivo. J. Virol. 74: 4433-4440 [Abstract] [Full Text]  
• Wang, J.-K., Kiyokawa, E., Verdin, E., Trono, D. (2000). The Nef protein of HIV-1 associates with rafts and primes T cells for activation. Proc. Natl. Acad. Sci. USA 97: 394-399 [Abstract] [Full Text]  
• An, D. S., Morizono, K., Li, Q.-X., Mao, S. H., Lu, S., Chen, I. S. Y. (1999). An Inducible Human Immunodeficiency Virus Type 1 (HIV-1) Vector Which Effectively Suppresses HIV-1 Replication. J. Virol. 73: 7671-7677 [Abstract] [Full Text]  
• Kovalev, G., Duus, K., Wang, L., Lee, R., Bonyhadi, M., Ho, D., McCune, J. M., Kaneshima, H., Su, L. (1999). Induction of MHC Class I Expression on Immature Thymocytes in HIV-1-Infected SCID-hu Thy/Liv Mice: Evidence of Indirect Mechanisms. J. Immunol. 162: 7555-7562 [Abstract] [Full Text]  
• Karlsson, G. B., Halloran, M., Schenten, D., Lee, J., Racz, P., Tenner-Racz, K., Manola, J., Gelman, R., Etemad-Moghadam, B., Desjardins, E., Wyatt, R., Gerard, N. P., Marcon, L., Margolin, D., Fanton, J., Axthelm, M. K., Letvin, N. L., Sodroski, J. (1998). The Envelope Glycoprotein Ectodomains Determine the Efficiency of CD4+ T Lymphocyte Depletion in Simian- Human Immunodeficiency Virus-Infected Macaques. J. Exp. Med. 188: 1159-1171 [Abstract] [Full Text]  
• Ishikawa, H., Sasaki, M., Noda, S., Koga, Y. (1998). Apoptosis Induction by the Binding of the Carboxyl Terminus of Human Immunodeficiency Virus Type 1 gp160 to Calmodulin. J. Virol. 72: 6574-6580 [Abstract] [Full Text]  
• Rao, P. V., Gallagher, T. M. (1998). Intracellular Complexes of Viral Spike and Cellular Receptor Accumulate during Cytopathic Murine Coronavirus Infections. J. Virol. 72: 3278-3288 [Abstract] [Full Text]