Microvirin, a novel alpha(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.
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(+) T cells and inhibits DC-SIGN-mediated HIV-1 binding and transmission to CD4(+) 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(+) 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.
Huskens
Dana
D
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Férir
Geoffrey
G
Vermeire
Kurt
K
Kehr
Jan-Christoph
JC
Balzarini
Jan
J
Dittmann
Elke
E
Schols
Dominique
D
D019380:Anti-HIV Agents / Q000494:pharmacology*; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000737:chemistry* / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D002352:Carrier Proteins / Q000494:pharmacology*; D002469:Cell Separation; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004353:Drug Evaluation, Preclinical; D005434:Flow Cytometry; D015497:HIV-1 / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D037102:Lectins / Q000737:chemistry*; D037181:Lectins, C-Type / Q000096:biosynthesis; D008358:Mannose / Q000737:chemistry*; D037601:Mannose-Binding Lectin / Q000737:chemistry* / Q000494:pharmacology; D046931:Microcystis / Q000378:metabolism*; D000099192:CD69 Antigens
D019380:Anti-HIV Agents; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D001426:Bacterial Proteins; D002352:Carrier Proteins; D006684:HLA-DR Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D037102:Lectins; D037181:Lectins, C-Type; D008358:Mannose; D037601:Mannose-Binding Lectin; D000099192:CD69 Antigens; C552210:microvirin protein, Microcystis aeruginosa; C107733:cyanovirin N