QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: mol.106.030155v1 71/1/3    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Balzarini, J. Articles by Schols, D. Search for Related Content PubMed PubMed Citation Articles by Balzarini, J. Articles by Schols, D.

Accelerated Communication

Carbohydrate-Binding Agents Efficiently Prevent Dendritic Cell-Specific Intercellular Adhesion Molecule-3-Grabbing Nonintegrin (DC-SIGN)-Directed HIV-1 Transmission to T Lymphocytes

Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium (J.B., K.V., D.S.); and Institute for Tropical Medicine, Antwerp, Belgium (Y.V.H., G.V.)

Exposure of HIV-1 to dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)-expressing B-lymphoblast Raji cells (Raji/DC-SIGN) but not to wild-type Raji/0 cells results in the capture of HIV-1 particles to the cells as measured by the quantification of cell-associated p24 antigen. Cocultivation of HIV-1-captured Raji/DC-SIGN cells with uninfected CD4⁺ T lymphocyte C8166 cells results in abundant formation of syncytia within 36 h after cocultivation. Short preexposure of HIV-1 to carbohydrate-binding agents (CBA) dose dependently prevents the Raji/DC-SIGN cells from efficiently binding the virus particles, and no syncytia formation occurs upon subsequent cocultivation with C8166 cells. Thus, the mannose-specific [i.e., the plant lectins Hippeastrum hybrid agglutinin (HHA), Galanthus nivalis agglutinin (GNA), Narcissus pseudonarcissus agglutinin; and Cymbidium agglutinin (CA); the procaryotic cyanovirin-N (CV-N); and the monoclonal antibody 2G12) and N-acetylglucosamine-specific (i.e., the plant lectin Urtica dioica agglutinin) CBAs efficiently abrogate the DC-SIGN-directed HIV-1 capture and subsequent transmission to T lymphocytes. In this assay, the CD4-down-regulating cyclotriazodisulfonamide derivative, the CXCR4 and CCR5 coreceptor antagonists 1-[[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl] - 1,4,8,11 - tetrazacyclotetradecane (AMD3100) and maraviroc, the gp41-binding enfuvirtide, and the polyanionic substances dextran sulfate (M_r 5000), sulfated polyvinyl alcohol, and the naphthalene sulfonate polymer PRO-2000 were markedly less efficient or even completely ineffective. Similar observations were made in primary monocyte-derived dendritic cell cultures that were infected with HIV-1 particles that had been shortly pre-exposed to the CBAs CV-N, CA, HHA, and GNA and the polyanions DS-5000 and PRO-2000. The potential of CBAs, but not polyanions and other structural/functional classes of entry inhibitors, to impair DC-SIGN-expressing cells in their capacity of transmitting HIV to T lymphocytes might be an important property to be taken into consideration in the eventual choice to move microbicide candidate drugs to the clinical setting.

Address correspondence to: Prof. Dr. Jan Balzarini, Rega Institute for Medical Research, K.U. Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. E-mail: jan.balzarini{at}rega.kuleuven.be

This article has been cited by other articles:

				E. Balestrieri, A. Ascolani, Y. Igarashi, T. Oki, A. Mastino, J. Balzarini, and B. Macchi Inhibition of Cell-to-Cell Transmission of Human T-Cell Lymphotropic Virus Type 1 In Vitro by Carbohydrate-Binding Agents Antimicrob. Agents Chemother., August 1, 2008; 52(8): 2771 - 2779. [Abstract] [Full Text] [PDF]

				K. O. Francois, J. Auwerx, D. Schols, and J. Balzarini Simian Immunodeficiency Virus Is Susceptible to Inhibition by Carbohydrate-Binding Agents in a Manner Similar to That of HIV: Implications for Further Preclinical Drug Development Mol. Pharmacol., August 1, 2008; 74(2): 330 - 337. [Abstract] [Full Text] [PDF]

				L. Van Damme, R. Govinden, F. M. Mirembe, F. Guedou, S. Solomon, M. L. Becker, B.S. Pradeep, A.K. Krishnan, M. Alary, B. Pande, et al. Lack of Effectiveness of Cellulose Sulfate Gel for the Prevention of Vaginal HIV Transmission N. Engl. J. Med., July 31, 2008; 359(5): 463 - 472. [Abstract] [Full Text] [PDF]

				N. Teleshova, T. Chang, A. Profy, and M. E. Klotman Inhibitory Effect of PRO 2000, a Candidate Microbicide, on Dendritic Cell-Mediated Human Immunodeficiency Virus Transfer Antimicrob. Agents Chemother., May 1, 2008; 52(5): 1751 - 1758. [Abstract] [Full Text] [PDF]

				Q. Wang and S. Pang An intercellular adhesion molecule-3 (ICAM-3) -grabbing nonintegrin (DC-SIGN) efficiently blocks HIV viral budding FASEB J, April 1, 2008; 22(4): 1055 - 1064. [Abstract] [Full Text] [PDF]