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 Bosch, B.
Right arrow Articles by Esté, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bosch, B.
Right arrow Articles by Esté, J. A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, October 2005, p. 4296-4304, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4296-4304.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Inhibition of Coreceptor-Independent Cell-to-Cell Human Immunodeficiency Virus Type 1 Transmission by a CD4-Immunoglobulin G2 Fusion Protein

Berta Bosch,1 Julià Blanco,1 Eduardo Pauls,1 Imma Clotet-Codina,1 Mercedes Armand-Ugón,1 Boyan Grigorov,2 Delphine Muriaux,2 Bonaventura Clotet,1 Jean-Luc Darlix,2 and José A. Esté1*

Retrovirology Laboratory irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, Spain,1 LaboRetro, Unité de Virologie Humaine, INSERM #412, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69 364 Lyon, France2

Received 29 March 2005/ Returned for modification 4 June 2005/ Accepted 28 July 2005

We have previously shown (J. Blanco et al., J. Biol. Chem. 279:51305-51314, 2004) that the contact between HIV producing cells and primary CD4+ T cells may induce the uptake of human immunodeficiency virus (HIV) particles by target cells in the absence of HIV envelope-mediated membrane fusion or productive HIV replication. HIV uptake by CD4+ T cells was dependent on cellular contacts mediated by the binding of gp120 to CD4 but was independent of the expression of the appropriate HIV coreceptor, CCR5 or CXCR4. Here, we have characterized the effect of agents blocking gp120 binding to CD4 on cell-to-cell HIV transmission. A recombinant CD4-based protein (CD4-immunoglobulin G2 [IgG2]), that is currently being evaluated in clinical trials, completely inhibited the uptake of HIV particles by CD4+ T cells from persistently infected cells expressing R5, X4, or X4/T-20-resistant HIV-1 envelope glycoproteins. Consequently, both the release of viral particles from endocytic vesicles and the infection of reporter U87-CD4 cells were also prevented. The polyanionic anti-HIV agent dextran sulfate failed to prevent the intracellular uptake of virions by CD4+ T cells. Indeed, it increased HIV uptake in a dose-dependent manner, suggesting functional differences between the specific gp120-targeting CD4-IgG2 agent and nonspecific HIV binding inhibitors. Thus, the inhibition of the specific interaction between gp120 and CD4 protein could be an effective strategy to inhibit HIV binding to CD4+ T cells, and the mechanism by which CD4+ T cells lacking the appropriate coreceptor may be converted in HIV carriers.

* Corresponding author. Mailing address: Fundació irsiCaixa, Laboratori de Retrovirologia, Hospital Universitari Germans Trias i Pujol, Ctra. Del Canyet s/n, 08916 Badalona, Spain. Phone: 34-934656374. Fax: 34-934653968. E-mail: jaeste{at}irsicaixa.es.

Antimicrobial Agents and Chemotherapy, October 2005, p. 4296-4304, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4296-4304.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Izquierdo-Useros, N., Blanco, J., Erkizia, I., Fernandez-Figueras, M. T., Borras, F. E., Naranjo-Gomez, M., Bofill, M., Ruiz, L., Clotet, B., Martinez-Picado, J. (2007). Maturation of Blood-Derived Dendritic Cells Enhances Human Immunodeficiency Virus Type 1 Capture and Transmission. J. Virol. 81: 7559-7570 [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]  
  • Pauls, E., Senserrich, J., Clotet, B., Este, J. A. (2006). Inhibition of HIV-1 replication by RNA interference of p53 expression. J. Leukoc. Biol. 80: 659-667 [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»