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Antimicrobial Agents and Chemotherapy, October 2004, p. 3858-3870, Vol. 48, No. 10
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.10.3858-3870.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Mannose-Specific Plant Lectins from the Amaryllidaceae Family Qualify as Efficient Microbicides for Prevention of Human Immunodeficiency Virus Infection

Jan Balzarini,1* Sigrid Hatse,1 Kurt Vermeire,1 Katrien Princen,1 Stefano Aquaro,2 Carlo-Federico Perno,2 Erik De Clercq,1 Herman Egberink,3 Guy Vanden Mooter,4 Willy Peumans,5 Els Van Damme,5 and Dominique Schols1

Rega Institute for Medical Research, Leuven,1 Laboratory Farmacotechnology Biopharmacy, Heverlee,4 Department of Molecular Biotechnology, RUGent, Ghent Belgium,5 Department of Experimental Medicine, University of Rome "Tor Vergata," Rome, Italy,2 Institute of Virology, Utrecht University, Utrecht, The Netherlands3

Received 28 May 2003/ Returned for modification 2 September 2003/ Accepted 11 May 2004

The plant lectins derived from Galanthus nivalis (Snowdrop) (GNA) and Hippeastrum hybrid (Amaryllis) (HHA) selectively inhibited a wide variety of human immunodeficiency virus type 1 (HIV-1) and HIV-2 strains and clinical (CXCR4- and CCR5-using) isolates in different cell types. They also efficiently inhibited infection of T lymphocytes by a variety of mutant virus strains. GNA and HHA markedly prevented syncytium formation between persistently infected HUT-78/HIV cells and uninfected T lymphocytes. The plant lectins did not measurably affect the antiviral activity of other clinically approved anti-HIV drugs used in the clinic when combined with these drugs. Short exposure of the lectins to cell-free virus particles or persistently HIV-infected HUT-78 cells markedly decreased HIV infectivity and increased the protective (microbicidal) activity of the plant lectins. Flow cytometric analysis and monoclonal antibody binding studies and a PCR-based assay revealed that GNA and HHA do not interfere with CD4, CXCR4, CCR5, and DC-SIGN and do not specifically bind with the membrane of uninfected cells. Instead, GNA and HHA likely interrupt the virus entry process by interfering with the virus envelope glycoprotein. HHA and GNA are odorless, colorless, and tasteless, and they are not cytotoxic, antimetabolically active, or mitogenic to human primary T lymphocytes at concentrations that exceed their antivirally active concentrations by 2 to 3 orders of magnitude. GNA and HHA proved stable at high temperature (50°C) and low pH (5.0) for prolonged time periods and can be easily formulated in gel preparations for microbicidal use; they did not agglutinate human erythrocytes and were not toxic to mice when administered intravenously.

* Corresponding author. Mailing address: Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Phone: 32-16-33-73-41. Fax: 32-16-33-73-40. E-mail: jan.balzarini{at}rega.kuleuven.ac.be.

Antimicrobial Agents and Chemotherapy, October 2004, p. 3858-3870, Vol. 48, No. 10
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.10.3858-3870.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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