HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 10, 9345-9353, March 11, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/10/9345    most recent M411122200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mori, T. Articles by Boyd, M. R. Search for Related Content PubMed PubMed Citation Articles by Mori, T. Articles by Boyd, M. R. Social Bookmarking                      What's this?

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

From the ^aMolecular Targets Development Program, Center for Cancer Research, NCI-Frederick, ^eAIDS Vaccine Program and ^fBasic Research Program, SAIC-Frederick, and ^gRetrovirus Research Laboratory, Southern Research Institute, Frederick, Maryland 21702

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.

Received for publication, September 28, 2004 , and in revised form, December 20, 2004.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AY744143 and AY744144.

^* This work was supported by NCI Grant NO1-CO-12400 from the National Institutes of Health. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^c Both authors contributed equally to this work.

^h Present address: NIAID, National Institutes of Health, Bethesda, MD 20892.

ⁱ Present address: ImQuest BioSciences, Inc, Frederick, MD 21704.

^j Present address: USA Cancer Research Institute, College of Medicine, University of South Alabama, Mobile, AL 36688.

^b To whom correspondence may be addressed: Molecular Targets Development Program, Center for Cancer Research, Bldg. 1052, Rm. 122, NCI-Fredrick, MD 21702. Tel.: 301-846-1830 Fax: 301-846-6177; E-mail: mori{at}ncifcrf.gov. ^d To whom correspondence may be addressed: Molecular Targets Development Program, Center for Cancer Research, Bldg. 562, Rm. 201, NCI-Fredrick, MD 21702. Tel.: 301-846-5332; Fax: 301-846-6919; E-mail: okeefe{at}ncifcrf.gov.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				B. R. O'Keefe, F. Vojdani, V. Buffa, R. J. Shattock, D. C. Montefiori, J. Bakke, J. Mirsalis, A.-L. d'Andrea, S. D. Hume, B. Bratcher, et al. From the Cover: Scaleable manufacture of HIV-1 entry inhibitor griffithsin and validation of its safety and efficacy as a topical microbicide component PNAS, April 14, 2009; 106(15): 6099 - 6104. [Abstract] [Full Text] [PDF]

				L. Zeitlin, M. Pauly, and K. J. Whaley Second-generation HIV microbicides: Continued development of griffithsin PNAS, April 14, 2009; 106(15): 6029 - 6030. [Full Text] [PDF]

				M. C. Skinner, W. E. Stamm, and M. L. Lampe Chlamydia trachomatis Laboratory Strains versus Recent Clinical Isolates: Implications for Routine Microbicide Testing Antimicrob. Agents Chemother., April 1, 2009; 53(4): 1482 - 1489. [Abstract] [Full Text] [PDF]

				K. Hori, Y. Sato, K. Ito, Y. Fujiwara, Y. Iwamoto, H. Makino, and A. Kawakubo Strict specificity for high-mannose type N-glycans and primary structure of a red alga Eucheuma serra lectin Glycobiology, May 1, 2007; 17(5): 479 - 491. [Abstract] [Full Text] [PDF]

				Y. Sato, S. Okuyama, and K. Hori Primary Structure and Carbohydrate Binding Specificity of a Potent Anti-HIV Lectin Isolated from the Filamentous Cyanobacterium Oscillatoria agardhii J. Biol. Chem., April 13, 2007; 282(15): 11021 - 11029. [Abstract] [Full Text] [PDF]