Microvirin, a Novel a(1,2)-Mannose-specific Lectin Isolated from Microcystis aeruginosa, Has Anti-HIV-1 Activity Comparable with That of Cyanovirin-N but a Much Higher Safety Profile

• Published in: The Journal of biological chemistry Vol. 285; no. 32; pp. 24845 - 24854
• Main Authors: Huskens, Dana, Ferir, Geoffrey, Vermeire, Kurt, Kehr, Jan-Christoph, Balzarini, Jan, Dittmann, Elke, Schols, Dominique
• Format: Journal Article
• Language: English
• Published: 06.08.2010
• Subjects: Cyanobacteria; Human immunodeficiency virus 1; Microcystis aeruginosa; Nostoc ellipsosporum
• ISSN: 0021-9258
• DOI: 10.1074/jbc.M110.128546

Microvirin (MVN), a recently isolated lectin from the cyanobacterium Microcystis aeruginosa PCC7806, shares 33% identity with the potent anti-human immunodeficiency virus (HIV) protein cyanovirin-N (CV-N) isolated from Nostoc ellipsosporum, and both lectins bind to similar carbohydrate structures. MVN is able to inhibit infection by a wide variety of HIV-1 laboratory-adapted strains and clinical isolates of different tropisms and subtypes in peripheral blood mononuclear cells. MVN also inhibits syncytium formation between persistently HIV-1-infected T cells and uninfected CD4 super(+) T cells and inhibits DC-SIGN-mediated HIV-1 binding and transmission to CD4 super(+) T cells. Long term passaging of HIV-1 exposed to dose-escalating concentrations of MVN resulted in the selection of a mutant virus with four deleted high mannose-type glycans in the envelope gp120. The MVN-resistant virus was still highly sensitive to various other carbohydrate binding lectins (e.g. CV-N, HHA, GNA, and UDA) but not anymore to the carbohydrate-specific 2G12 monoclonal antibody. Importantly, MVN is more than 50-fold less cytotoxic than CV-N. Also in sharp contrast to CV-N, MVN did not increase the level of the activation markers CD25, CD69, and HLA-DR in CD4 super(+) T lymphocytes, and subsequently, MVN did not enhance viral replication in pretreated peripheral blood mononuclear cells. Therefore, MVN may qualify as a useful lectin for potential microbicidal use based on its broad and potent antiviral activity and virtual lack of any stimulatory properties and cellular toxicity.