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Please use this identifier to cite or link to this item: http://hdl.handle.net/10204/5790

Title: UCLA1, a synthetic derivative of a gp120 RNA aptamer, inhibits entry of human immunodeficiency virus type 1 subtype C
Authors: Mufhandu, HT
Gray, ES
Madiga, MC
Tumba, N
Alexandre, KB
Khoza, T
Wibmer, CK
Moore, PL
Morris, L
Khati, M
Keywords: HIV-1
UCLA1
gp120
Inhibitor drugs
Aptamers
Issue Date: May-2012
Publisher: American Society for Microbiology
Citation: Mufhandu, HT, Gray, ES, Madiga, MC, Tumba, N, Alexandre, KB, Khoza, T, Wibmer, CK, Moore, PL, Morris, L and Khati, M. 2012. UCLA1, a synthetic derivative of a gp120 RNA aptamer, inhibits entry of human immunodeficiency virus type 1 subtype C. Journal of Virology, vol. 86(9), pp 4989-4999
Series/Report no.: Workflow;3129
Abstract: Entry of human immunodeficiency virus type 1 (HIV-1) into cells is mediated by the virion surface envelope (Env) glycoproteins, making it a desirable target for antiretroviral entry inhibitors. We previously isolated a family of gp120 binding RNA aptamers and showed that they neutralized the infectivity of HIV-1. In this study, we assessed the activity of a shortened synthetic derivative of the B40 aptamer, called UCLA1, against a large panel of HIV-1 subtype C viruses. UCLA1 tightly bound to a consensus HIV-1 subtype C gp120 and neutralized isolates of the same subtype with 50% inhibitory concentrations (IC50s) in the nanomolar range. The aptamer had little toxicity in tests with cell lines and primary cells. Furthermore, it exhibited high therapeutic indices, suggesting that it may be effective at very low doses. Mapping of UCLA1 binding sites on gp120 revealed eight amino acid residues that modulated neutralization resistance. This included residues within the coreceptor binding site, at the base of the V3 loop, and in the bridging sheet within the conserved V1/V2 stem-loop of gp120. The aptamer was also shown to have synergistic effects with T20, a gp41 fusion inhibitor, and IgG1b12 (b12), an anti-CD4 binding site monoclonal antibody. These results suggest that UCLA1 may be suitable for development as a potent HIV-1 entry inhibitor.
Description: Copyright: 2012, American Society for Microbiology. This is the accepted version of the work. The definitive version is published in Journal of Virology, vol. 86(9), pp 4989-4999
URI: http://jvi.asm.org/content/early/2012/02/22/JVI.06893-11.full.pdf+html
http://jvi.asm.org/content/early/2012/02/22/JVI.06893-11.abstract
http://hdl.handle.net/10204/5790
ISSN: 0022-538X
Appears in Collections:General science, engineering & technology
Aptamer technology

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