Mannose-specific plant lectins from the Amaryllidaceae family qualify as efficient microbicides for prevention of human immunodeficiency virus infection

Jan Balzarini, Sigrid Hatse, Kurt Vermeire, Katrien Princen, Stefano Aquaro, Carlo Federico Perno, Erik De Clercq, Herman Egberink, Guy Vanden Mooter, Willy Peumans, Els Van Damme, Dominique Schols

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3858-3870
Number of pages13
JournalAntimicrobial Agents and Chemotherapy
Volume48
Issue number10
DOIs
Publication statusPublished - Oct 2004

Fingerprint

Mannose-Binding Lectins
Plant Lectins
Virus Diseases
Anti-Infective Agents
HIV
Galanthus
T-Lymphocytes
Viruses
Anti-HIV Agents
Virus Internalization
HIV-2
Poisons
Giant Cells
Lectins
Virion
Antiviral Agents
Amaryllidaceae
HIV-1
Glycoproteins
Erythrocytes

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Mannose-specific plant lectins from the Amaryllidaceae family qualify as efficient microbicides for prevention of human immunodeficiency virus infection. / Balzarini, Jan; Hatse, Sigrid; Vermeire, Kurt; Princen, Katrien; Aquaro, Stefano; Perno, Carlo Federico; De Clercq, Erik; Egberink, Herman; Vanden Mooter, Guy; Peumans, Willy; Van Damme, Els; Schols, Dominique.

In: Antimicrobial Agents and Chemotherapy, Vol. 48, No. 10, 10.2004, p. 3858-3870.

Research output: Contribution to journalArticle

Balzarini, J, Hatse, S, Vermeire, K, Princen, K, Aquaro, S, Perno, CF, De Clercq, E, Egberink, H, Vanden Mooter, G, Peumans, W, Van Damme, E & Schols, D 2004, 'Mannose-specific plant lectins from the Amaryllidaceae family qualify as efficient microbicides for prevention of human immunodeficiency virus infection', Antimicrobial Agents and Chemotherapy, vol. 48, no. 10, pp. 3858-3870. https://doi.org/10.1128/AAC.48.10.3858-3870.2004
Balzarini, Jan ; Hatse, Sigrid ; Vermeire, Kurt ; Princen, Katrien ; Aquaro, Stefano ; Perno, Carlo Federico ; De Clercq, Erik ; Egberink, Herman ; Vanden Mooter, Guy ; Peumans, Willy ; Van Damme, Els ; Schols, Dominique. / Mannose-specific plant lectins from the Amaryllidaceae family qualify as efficient microbicides for prevention of human immunodeficiency virus infection. In: Antimicrobial Agents and Chemotherapy. 2004 ; Vol. 48, No. 10. pp. 3858-3870.
@article{8f827cf8ca7a4b7ba4638f11495059d4,
title = "Mannose-specific plant lectins from the Amaryllidaceae family qualify as efficient microbicides for prevention of human immunodeficiency virus infection",
abstract = "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.",
author = "Jan Balzarini and Sigrid Hatse and Kurt Vermeire and Katrien Princen and Stefano Aquaro and Perno, {Carlo Federico} and {De Clercq}, Erik and Herman Egberink and {Vanden Mooter}, Guy and Willy Peumans and {Van Damme}, Els and Dominique Schols",
year = "2004",
month = "10",
doi = "10.1128/AAC.48.10.3858-3870.2004",
language = "English",
volume = "48",
pages = "3858--3870",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "10",

}

TY - JOUR

T1 - Mannose-specific plant lectins from the Amaryllidaceae family qualify as efficient microbicides for prevention of human immunodeficiency virus infection

AU - Balzarini, Jan

AU - Hatse, Sigrid

AU - Vermeire, Kurt

AU - Princen, Katrien

AU - Aquaro, Stefano

AU - Perno, Carlo Federico

AU - De Clercq, Erik

AU - Egberink, Herman

AU - Vanden Mooter, Guy

AU - Peumans, Willy

AU - Van Damme, Els

AU - Schols, Dominique

PY - 2004/10

Y1 - 2004/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=4644227155&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4644227155&partnerID=8YFLogxK

U2 - 10.1128/AAC.48.10.3858-3870.2004

DO - 10.1128/AAC.48.10.3858-3870.2004

M3 - Article

C2 - 15388446

AN - SCOPUS:4644227155

VL - 48

SP - 3858

EP - 3870

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

IS - 10

ER -