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 Schaeffer, E.
Right arrow Articles by Greene, W. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schaeffer, E.
Right arrow Articles by Greene, W. C.

 Previous Article  |  Next Article 

Journal of Virology, February 2004, p. 1375-1383, Vol. 78, No. 3
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.3.1375-1383.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Compensatory Link between Fusion and Endocytosis of Human Immunodeficiency Virus Type 1 in Human CD4 T Lymphocytes

Evelyne Schaeffer,1,2 Vanessa B. Soros,1 and Warner C. Greene1,3*

Gladstone Institute of Virology and Immunology,1 Departments of Medicine and of Microbiology and Immunology, University of California, San Francisco, California 94141,3 Unité 575 INSERM, 67084 Strasbourg, France2

Received 1 May 2003/ Accepted 10 October 2003

Virions of the type 1 human immunodeficiency virus (HIV-1) can enter target cells by fusion or endocytosis, with sharply different functional consequences. Fusion promotes productive infection of the target cell, while endocytosis generally leads to virion inactivation in acidified endosomes or degradation in lysosomes. Virion fusion and endocytosis occur equally in T cells, but these pathways have been regarded as independent because endocytosis of HIV virions requires neither CD4 nor CCR5/CXCR4 engagement in HeLa-CD4 cells. Using flow cytometric techniques to assess the binding and entry of green fluorescent protein (GFP)-Vpr-labeled HIV virions into primary peripheral blood mononuclear cells, we have found that HIV fusion and endocytosis are restricted to the CD4-expressing subset of cells and that both pathways commonly require the initial binding of HIV virions to surface CD4 receptors. Blockade of CXCR4-tropic HIV virion fusion with AMD3100, a CXCR4-specific entry inhibitor, increased virion entry via the endocytic pathway. Similarly, inhibition of endosome acidification with bafilomycin A1, concanamycin A, or NH4Cl enhanced entry via the fusion pathway. Although fusion remained dependent on CD4 and chemokine receptor binding, the endosome inhibitors did not alter surface expression of CD4 and CXCR4. These results suggest that fusion in the presence of the endosome inhibitors likely occurs within nonacidified endosomes. However, the ability of these inhibitors to impair vesicle trafficking from early to late endosomes in some cells could also increase the recycling of these virion-containing endosomes to the cell surface, where fusion occurs. In summary, our results reveal an unexpected, CD4-mediated reciprocal relationship between the pathways governing HIV virion fusion and endocytosis.

* Corresponding author. Mailing address: Gladstone Institute of Virology and Immunology, P.O. Box 419100, San Francisco, CA 94141-9100. Phone: (415) 695-3800. Fax: (415) 826-1817. E-mail: wgreene{at}gladstone.ucsf.edu.

Journal of Virology, February 2004, p. 1375-1383, Vol. 78, No. 3
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.3.1375-1383.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Hubner, W., McNerney, G. P., Chen, P., Dale, B. M., Gordon, R. E., Chuang, F. Y. S., Li, X.-D., Asmuth, D. M., Huser, T., Chen, B. K. (2009). Quantitative 3D Video Microscopy of HIV Transfer Across T Cell Virological Synapses. Science 323: 1743-1747 [Abstract] [Full Text]  
  • Ruggiero, E., Bona, R., Muratori, C., Federico, M. (2008). Virological Consequences of Early Events following Cell-Cell Contact between Human Immunodeficiency Virus Type 1-Infected and Uninfected CD4+ Cells. J. Virol. 82: 7773-7789 [Abstract] [Full Text]  
  • Huang, J.-H., Qi, Z., Wu, F., Kotula, L., Jiang, S., Chen, Y.-H. (2008). Interaction of HIV-1 gp41 Core with NPF Motif in Epsin: IMPLICATION IN ENDOCYTOSIS OF HIV. J. Biol. Chem. 283: 14994-15002 [Abstract] [Full Text]  
  • Alvarez, R., Reading, J., King, D. F. L., Hayes, M., Easterbrook, P., Farzaneh, F., Ressler, S., Yang, F., Rowley, D., Vyakarnam, A. (2008). WFDC1/ps20 Is a Novel Innate Immunomodulatory Signature Protein of Human Immunodeficiency Virus (HIV)-Permissive CD4+ CD45RO+ Memory T Cells That Promotes Infection by Upregulating CD54 Integrin Expression and Is Elevated in HIV Type 1 Infection. J. Virol. 82: 471-486 [Abstract] [Full Text]  
  • Chen, P., Hubner, W., Spinelli, M. A., Chen, B. K. (2007). Predominant Mode of Human Immunodeficiency Virus Transfer between T Cells Is Mediated by Sustained Env-Dependent Neutralization-Resistant Virological Synapses. J. Virol. 81: 12582-12595 [Abstract] [Full Text]  
  • Sacha, J. B., Chung, C., Reed, J., Jonas, A. K., Bean, A. T., Spencer, S. P., Lee, W., Vojnov, L., Rudersdorf, R., Friedrich, T. C., Wilson, N. A., Lifson, J. D., Watkins, D. I. (2007). Pol-Specific CD8+ T Cells Recognize Simian Immunodeficiency Virus-Infected Cells Prior to Nef-Mediated Major Histocompatibility Complex Class I Downregulation. J. Virol. 81: 11703-11712 [Abstract] [Full Text]  
  • Dong, C., Janas, A. M., Wang, J.-H., Olson, W. J., Wu, L. (2007). Characterization of Human Immunodeficiency Virus Type 1 Replication in Immature and Mature Dendritic Cells Reveals Dissociable cis- and trans-Infection. J. Virol. 81: 11352-11362 [Abstract] [Full Text]  
  • Muratori, C., Sistigu, A., Ruggiero, E., Falchi, M., Bacigalupo, I., Palladino, C., Toschi, E., Federico, M. (2007). Macrophages Transmit Human Immunodeficiency Virus Type 1 Products to CD4-Negative Cells: Involvement of Matrix Metalloproteinase 9. J. Virol. 81: 9078-9087 [Abstract] [Full Text]  
  • Finnegan, C. M., Rawat, S. S., Cho, E. H., Guiffre, D. L., Lockett, S., Merrill, A. H. Jr., Blumenthal, R. (2007). Sphingomyelinase Restricts the Lateral Diffusion of CD4 and Inhibits Human Immunodeficiency Virus Fusion. J. Virol. 81: 5294-5304 [Abstract] [Full Text]  
  • Wang, J.-H., Janas, A. M., Olson, W. J., KewalRamani, V. N., Wu, L. (2007). CD4 Coexpression Regulates DC-SIGN-Mediated Transmission of Human Immunodeficiency Virus Type 1. J. Virol. 81: 2497-2507 [Abstract] [Full Text]  
  • Sourisseau, M., Sol-Foulon, N., Porrot, F., Blanchet, F., Schwartz, O. (2007). Inefficient Human Immunodeficiency Virus Replication in Mobile Lymphocytes. J. Virol. 81: 1000-1012 [Abstract] [Full Text]  
  • Vidricaire, G., Tremblay, M. J. (2005). Rab5 and Rab7, but Not ARF6, Govern the Early Events of HIV-1 Infection in Polarized Human Placental Cells. J. Immunol. 175: 6517-6530 [Abstract] [Full Text]  
  • Jones, K. S., Petrow-Sadowski, C., Bertolette, D. C., Huang, Y., Ruscetti, F. W. (2005). Heparan Sulfate Proteoglycans Mediate Attachment and Entry of Human T-Cell Leukemia Virus Type 1 Virions into CD4+ T Cells. J. Virol. 79: 12692-12702 [Abstract] [Full Text]  
  • Wei, B. L., Denton, P. W., O'Neill, E., Luo, T., Foster, J. L., Garcia, J. V. (2005). Inhibition of Lysosome and Proteasome Function Enhances Human Immunodeficiency Virus Type 1 Infection. J. Virol. 79: 5705-5712 [Abstract] [Full Text]  
  • Reeves, J. D., Lee, F.-H., Miamidian, J. L., Jabara, C. B., Juntilla, M. M., Doms, R. W. (2005). Enfuvirtide Resistance Mutations: Impact on Human Immunodeficiency Virus Envelope Function, Entry Inhibitor Sensitivity, and Virus Neutralization. J. Virol. 79: 4991-4999 [Abstract] [Full Text]  
  • Platt, E. J., Durnin, J. P., Kabat, D. (2005). Kinetic Factors Control Efficiencies of Cell Entry, Efficacies of Entry Inhibitors, and Mechanisms of Adaptation of Human Immunodeficiency Virus. J. Virol. 79: 4347-4356 [Abstract] [Full Text]  
  • Daecke, J., Fackler, O. T., Dittmar, M. T., Krausslich, H.-G. (2005). Involvement of Clathrin-Mediated Endocytosis in Human Immunodeficiency Virus Type 1 Entry. J. Virol. 79: 1581-1594 [Abstract] [Full Text]  
  • Yonezawa, A., Cavrois, M., Greene, W. C. (2005). Studies of Ebola Virus Glycoprotein-Mediated Entry and Fusion by Using Pseudotyped Human Immunodeficiency Virus Type 1 Virions: Involvement of Cytoskeletal Proteins and Enhancement by Tumor Necrosis Factor Alpha. J. Virol. 79: 918-926 [Abstract] [Full Text]  
  • Blanco, J., Bosch, B., Fernandez-Figueras, M. T., Barretina, J., Clotet, B., Este, J. A. (2004). High Level of Coreceptor-independent HIV Transfer Induced by Contacts between Primary CD4 T Cells. J. Biol. Chem. 279: 51305-51314 [Abstract] [Full Text]  
  • Vidricaire, G., Imbeault, M., Tremblay, M. J. (2004). Endocytic Host Cell Machinery Plays a Dominant Role in Intracellular Trafficking of Incoming Human Immunodeficiency Virus Type 1 in Human Placental Trophoblasts. J. Virol. 78: 11904-11915 [Abstract] [Full Text]  
  • Finnegan, C. M., Rawat, S. S., Puri, A., Wang, J. M., Ruscetti, F. W., Blumenthal, R. (2004). Ceramide, a target for antiretroviral therapy. Proc. Natl. Acad. Sci. USA 101: 15452-15457 [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»