Abstract
Griffithsin (GRFT), a novel anti-HIV protein, was isolated from an aqueous extract of the red alga Griffithsia sp. The 121-amino acid sequence of GRFT has been determined, and biologically active GRFT was subsequently produced by expression of a corresponding DNA sequence in Escherichia coli. Both native and recombinant GRFT displayed potent antiviral activity against laboratory strains and primary isolates of T- and M- tropic HIV-1 with EC50 values ranging from 0.043 to 0.63 nM. GRFT also aborted cell-to-cell fusion and transmission of HIV-1 infection at similar concentrations. High concentrations (e.g. 783 nM) of GRFT were not lethal to any tested host cell types. GRFT blocked CD4-dependent glycoprotein (gp) 120 binding to receptor-expressing cells and bound to viral coat glycoproteins (gp120, gp41, and gp160) in a glycosylation-dependent manner. GRFT preferentially inhibited gp120 binding of the monoclonal antibody (mAb) 2G12, which recognizes a carbohydrate-dependent motif, and the (mAb) 48d, which binds to CD4-induced epitope. In addition, GRFT moderately interfered with the binding of gp120 to sCD4. Further data showed that the binding of GRFT to soluble gp120 was inhibited by the monosaccharides glucose, mannose, and N-acetylglucosamine but not by galactose, xylose, fucose, N-acetylgalactosamine, or sialic acid-containing glycoproteins. Taken together these data suggest that GRFT is a new type of lectin that binds to various viral glycoproteins in a monosaccharide-dependent manner. GRFT could be a potential candidate microbicide to prevent the sexual transmission of HIV and AIDS.
Highlights
More than 40 million people are infected with HIV,1 type 1, worldwide [1]
Isolation and Structure Determination—The present study originated from observations of anti-HIV activity (EC50 Յ 2 g/ml) in a crude aqueous extract of the red alga Griffithsia in the primary in vitro anti-HIV screening assay from NCI [18]
The antibodies modestly cross-reacted with higher molecular mass protein(s) at around 26 kDa in a crude aqueous extract of the red alga Griffithsia
Summary
Vol 280, No 10, Issue of March 11, pp. 9345–9353, 2005 Printed in U.S.A. Isolation and Characterization of Griffithsin, a Novel HIV-inactivating Protein, from the Red Alga Griffithsia sp.*. Griffithsin (GRFT), a novel anti-HIV protein, was isolated from an aqueous extract of the red alga Griffithsia sp. Our laboratory has been interested in the elucidation of protein and peptide leads that might reveal unprecedented mechanisms of anti-HIV activity and/or serve as templates for discovery and development of novel, small molecule inhibitors of HIV infection [9]. Such leads are potentially attractive for microbicide development. We describe the isolation and characterization of the novel, potent anti-HIV protein, griffithsin (GRFT), from the aqueous extract of Griffithsia sp.
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