Isolation and Characterization of Griffithsin, a Novel HIV-inactivating Protein, from the Red Alga Griffithsia sp. Export

@article{citeulike:5720252, 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. 10.1074/jbc.M411122200}, author = {Mori, Toshiyuki and O'Keefe, Barry R. and Sowder, Raymond C. and Bringans, Scott and Gardella, Roberta and Berg, Shannon and Cochran, Pamela and Turpin, Jim A. and Buckheit, Robert W. and Mcmahon, James B. and Boyd, Michael R.}, citeulike-article-id = {5720252}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M411122200}, citeulike-linkout-1 = {http://www.jbc.org/cgi/content/abstract/280/10/9345}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/15613479}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=15613479}, day = {11}, doi = {10.1074/jbc.M411122200}, journal = {J. Biol. Chem.}, keywords = {griffithsin, hiv, lectin}, month = {March}, number = {10}, pages = {9345--9353}, posted-at = {2009-09-04 00:03:12}, priority = {2}, title = {Isolation and Characterization of Griffithsin, a Novel HIV-inactivating Protein, from the Red Alga Griffithsia sp.}, url = {http://dx.doi.org/10.1074/jbc.M411122200}, volume = {280}, year = {2005} }

TY - JOUR ID - citeulike:5720252 L3 - citeulike-article-id:5720252 N2 - 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. 10.1074/jbc.M411122200 IS - 10 JF - J. Biol. Chem. EP - 9353 TI - Isolation and Characterization of Griffithsin, a Novel HIV-inactivating Protein, from the Red Alga Griffithsia sp. VL - 280 SP - 9345 KW - griffithsin KW - hiv KW - lectin AU - Mori, Toshiyuki AU - O'Keefe, Barry AU - Sowder, Raymond AU - Bringans, Scott AU - Gardella, Roberta AU - Berg, Shannon AU - Cochran, Pamela AU - Turpin, Jim AU - Buckheit, Robert AU - Mcmahon, James AU - Boyd, Michael PY - 2005/03/11/ UR - http://dx.doi.org/10.1074/jbc.M411122200 ER -