An aptamer that neutralizes R5 strains of human immunodeficiency virus type 1 blocks gp120-CCR5 interaction.
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.
Dey
Antu K
AK
Laboratory of Molecular Biophysics, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom.
Khati
Makobetsa
M
Tang
Min
M
Wyatt
Richard
R
Lea
Susan M
SM
James
William
W
D019380:Anti-HIV Agents / Q000494:pharmacology; D052157:Aptamers, Nucleotide; D001665:Binding Sites / Q000187:drug effects; D015699:HIV Envelope Protein gp120 / Q000187:drug effects / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D012313:RNA / Q000494:pharmacology*; D019713:Receptors, CCR5 / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D014779:Virus Replication
D019380:Anti-HIV Agents; D052157:Aptamers, Nucleotide; D015699:HIV Envelope Protein gp120; C502124:RNA aptamer B40; D019713:Receptors, CCR5; D012313:RNA