This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by O'Keefe, B. R.
Right arrow Articles by Boyd, M. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by O'Keefe, B. R.
Right arrow Articles by Boyd, M. R.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, August 2003, p. 2518-2525, Vol. 47, No. 8
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.8.2518-2525.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Potent Anti-Influenza Activity of Cyanovirin-N and Interactions with Viral Hemagglutinin

Barry R. O'Keefe,1 Donald F. Smee,2 Jim A. Turpin,3,{dagger} Carrie J. Saucedo,4 Kirk R. Gustafson,1 Toshiyuki Mori,1 Dennis Blakeslee,5 Robert Buckheit,3,{ddagger} and Michael R. Boyd6*

Molecular Targets Development Program, Center for Cancer Research,1 Basic Research Program, SAIC-Frederick, Inc., National Cancer Institute-Frederick,4 Retrovirus Research Laboratory, Southern Research Institute, Frederick, Maryland 21702,3 Institute for Antiviral Research, Utah State University, Logan, Utah 84322,2 Omniviral Therapeutics, LLC, Germantown, Maryland 20874,5 USA Cancer Research Institute, College of Medicine, University of South Alabama, Mobile, Alabama 366886

Received 31 October 2002/ Returned for modification 22 January 2003/ Accepted 23 May 2003

The novel antiviral protein cyanovirin-N (CV-N) was initially discovered based on its potent activity against the human immunodeficiency virus (HIV). Subsequent studies identified the HIV envelope glycoproteins gp120 and gp41 as molecular targets of CV-N. More recently, mechanistic studies have shown that certain high-mannose oligosaccharides (oligomannose-8 and oligomannose-9) found on the HIV envelope glycoproteins comprise the specific sites to which CV-N binds. Such selective, carbohydrate-dependent interactions may account, at least in part, for the unusual and unexpected spectrum of antiviral activity of CV-N described herein. We screened CV-N against a broad range of respiratory and enteric viruses, as well as flaviviruses and herpesviruses. CV-N was inactive against rhinoviruses, human parainfluenza virus, respiratory syncytial virus, and enteric viruses but was moderately active against some herpesvirus and hepatitis virus (bovine viral diarrhea virus) strains (50% effective concentration [EC50] = ~1 µg/ml) while inactive against others. Remarkably, however, CV-N and related homologs showed highly potent antiviral activity against almost all strains of influenza A and B virus, including clinical isolates and a neuraminidase inhibitor-resistant strain (EC50 = 0.004 to 0.04 µg/ml). When influenza virus particles were pretreated with CV-N, viral titers were lowered significantly (>1,000-fold). Further studies identified influenza virus hemagglutinin as a target for CV-N, showed that antiviral activity and hemagglutinin binding were correlated, and indicated that CV-N's interactions with hemagglutinin involved oligosaccharides. These results further reveal new potential avenues for antiviral therapeutics and prophylaxis targeting specific oligosaccharide-comprised sites on certain enveloped viruses, including HIV, influenza virus, and possibly others.

* Corresponding author. Mailing address: College of Medicine, CSAB 170, University of South Alabama, Mobile, AL 36688-0002. Phone: (251) 460-7189. Fax: (251) 460-6073. E-mail: mboyd{at}usouthal.edu.

{dagger} Present address: HowPin International Consulting, Frederick, MD 21705.

{ddagger} Present address: TherImmune Research Corporation, Gaithersburg, MD 20879.

Antimicrobial Agents and Chemotherapy, August 2003, p. 2518-2525, Vol. 47, No. 8
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.8.2518-2525.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Barrientos, L. G., Matei, E., Lasala, F., Delgado, R., Gronenborn, A. M. (2006). Dissecting carbohydrate-Cyanovirin-N binding by structure-guided mutagenesis: functional implications for viral entry inhibition. Protein Eng Des Sel 19: 525-535 [Abstract] [Full Text]  
  • Helle, F., Wychowski, C., Vu-Dac, N., Gustafson, K. R., Voisset, C., Dubuisson, J. (2006). Cyanovirin-N Inhibits Hepatitis C Virus Entry by Binding to Envelope Protein Glycans. J. Biol. Chem. 281: 25177-25183 [Abstract] [Full Text]  
  • Mori, T., O'Keefe, B. R., Sowder, R. C. II, Bringans, S., Gardella, R., Berg, S., Cochran, P., Turpin, J. A., Buckheit, R. W. Jr., McMahon, J. B., Boyd, M. R. (2005). Isolation and Characterization of Griffithsin, a Novel HIV-inactivating Protein, from the Red Alga Griffithsia sp.. J. Biol. Chem. 280: 9345-9353 [Abstract] [Full Text]  
  • Yasin, B., Wang, W., Pang, M., Cheshenko, N., Hong, T., Waring, A. J., Herold, B. C., Wagar, E. A., Lehrer, R. I. (2004). {theta} Defensins Protect Cells from Infection by Herpes Simplex Virus by Inhibiting Viral Adhesion and Entry. J. Virol. 78: 5147-5156 [Abstract] [Full Text]  
  • McSharry, J. J., McDonough, A. C., Olson, B. A., Drusano, G. L. (2004). Phenotypic Drug Susceptibility Assay for Influenza Virus Neuraminidase Inhibitors. CVI 11: 21-28 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»