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Journal of Virology, November 2005, p. 13806-13810, Vol. 79, No. 21
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.21.13806-13810.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

An Aptamer That Neutralizes R5 Strains of Human Immunodeficiency Virus Type 1 Blocks gp120-CCR5 Interaction

Antu K. Dey,^1,2, Makobetsa Khati,^2, Min Tang,³ Richard Wyatt,³ Susan M. Lea,¹ and William James^2*

Laboratory of Molecular Biophysics, Department of Biochemistry,¹ Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, United Kingdom,² Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892³

Received 5 April 2005/ Accepted 3 August 2005

We recently described the isolation and structural characterization of 2'-fluoropyrimidine-substituted RNA aptamers that bind to gp120 of R5 strains of human immunodeficiency virus type 1 and thereby potently neutralize the infectivity of phylogenetically diverse R5 strains. Here we investigate the physical basis of their antiviral action. We show that both N-linked oligosaccharides and the variable loops V1/V2 and V3 are not required for binding of one aptamer, B40, to gp120. Using surface plasmon resonance binding analyses, we show that the aptamer binds to the CCR5-binding site on gp120 in a relatively CD4-independent manner, providing a mechanistic explanation for its neutralizing potency.

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* Corresponding author. Mailing address: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom. Phone: 44(1865) 275548. Fax: 44(1865) 285756. E-mail: william.james{at}pathology.oxford.ac.uk.

Present address: Department of Microbiology and Immunology, Weill Medical College, Cornell University, New York, NY 10021.

Present address: Institute of Infectious Disease and Molecular Medicine, UCT Medical School, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa.

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Journal of Virology, November 2005, p. 13806-13810, Vol. 79, No. 21
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.21.13806-13810.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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