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Journal of Virology, December 2003, p. 12692-12698, Vol. 77, No. 23
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.23.12692-12698.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Neutralization of Infectivity of Diverse R5 Clinical Isolates of Human Immunodeficiency Virus Type 1 by gp120-Binding 2'F-RNA Aptamers

Makobetsa Khati,1 Michael Schüman,1 Jamal Ibrahim,1 Quentin Sattentau,2 Siamon Gordon,1 and William James1*

Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE,1 The Jefferiss Trust Laboratories, The Wright-Fleming Institute, Imperial College Faculty of Medicine, London W2 1PG, United Kingdom2

Received 31 March 2003/ Accepted 20 August 2003

Human immunodeficiency virus type 1 (HIV-1) has evolved a number of strategies to resist current antiretroviral drugs and the selection pressures of humoral and cellular adaptive immunity. For example, R5 strains, which use the CCR5 coreceptor for entry and are the dominant viral phenotype for HIV-1 transmission and AIDS pathogenesis, are relatively resistant to neutralization by antibodies, as are other clinical isolates. In order to overcome these adaptations, we raised nucleic acid aptamers to the SU glycoprotein (gp120) of the R5 strain, HIV-1Ba-L. These not only bound gp120 with high affinity but also neutralized HIV-1 infectivity in human peripheral blood mononuclear cells (PBMCs) by more than 1,000-fold. Furthermore, these aptamers were able to neutralize the infectivity of R5 clinical isolates of HIV-1 derived from group M (subtypes A, C, D, E, and F) and group O. One aptamer defined a site on gp120 that overlaps partially with the conserved, chemokine receptor-binding, CD4-induced epitope recognized by monoclonal antibody 17b. In contrast to the antibody, the site is accessible to aptamer in the absence of CD4 binding. Neutralizing aptamers such as this could be exploited to provide leads in developing alternative, efficacious anti-HIV-1 drugs and lead to a deeper understanding of the molecular interactions between the virus and its host cell.

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

Journal of Virology, December 2003, p. 12692-12698, Vol. 77, No. 23
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.23.12692-12698.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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