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

Journal of Virology - Tập 79 Số 21 - Trang 13806-13810 - 2005
Antu Dey1,2, Makobetsa Khati2, Min Tang3, Richard T. Wyatt3, Susan M. Lea1, William James2
1Laboratory of Molecular Biophysics, Department of Biochemistry
2Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, United Kingdom
3Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892

Tóm tắt

ABSTRACT 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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Journal of Virology

Tập 79 Số 21

13806-13810

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