Microvirin, a novel α(1,2)-mannose-specific lectin isolated from Microcystis aeruginosa, has potent anti-HIV-1 activity

The most effective approach to halt the HIV epidemic will be establishing effective prevention methods incorporating multiple types of intervention including among others anti-HIV microbicides. Microvirin (MVN), a recently isolated lectin from the cyanobacterium Microcystis aeruginosa PCC7806, shares 33% identity with the potent anti-HIV protein cyanovirin-N (CV-N) isolated from Nostoc ellipsosporum and both carbohydrate binding agents (CBAs) bind to similar carbohydrate structures. MVN is able to inhibit infection by a wide variety of HIV-1 laboratory-adapted strains and various clinical isolates of different tropisms and subtypes in peripheral blood mononuclear cells (PBMCs) (IC50: 2-167 nM). MVN also inhibits syncytium formation between persistently HIV-1-infected T cells and uninfected CD4+ T cells (IC50: 124 nM). It also inhibits DC-SIGN-mediated HIV-1 binding (IC50: 189 nM) and subsequent transmission to CD4+ T cells (IC50: 168 nM). Long term passaging of HIV-1 exposed to dose-escalating concentrations of MVN resulted in the selection of a mutant virus with 4 deleted high-mannose-type glycans in the envelope gp120 (T297I, T341(T,I), N386(K,N), N392D). The MVN-resistant virus was still highly sensitive to various other CBAs (e.g. CV-N, HHA, GNA and UDA), but not anymore to the carbohydrate-specific 2G12 mAb. Importantly, MVN is more than 50-fold less cytotoxic than CV-N with CC50 values of >35 µM and >7 µM in MT-4 cells and PBMCs, respectively. Also in sharp contrast to CV-N, MVN did not increase the level of the cellular activation markers CD25, CD69 and HLA-DR in freshly-isolated CD4+ T lymphocytes. MVN did not enhance viral replication in pre-treated PBMCs as was observed with several other CBAs. 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. Suggested Reference: HUSKENS, D., FÉRIR, G., VERMEIRE, K., KEHR, J.-C., BALZARINI, J., DITTMANN, E., and SCHOLS, D. (2010) J. Biol. Chem. 285: 24845-24854status: publishe