ES Gray

HT Mufhandu

KB Alexandre

L Morris

M Khati

PubMed

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POSTER PRESENTATION Open Access
HIV-1 subtype C primary isolates exhibit high
sensitivity to an anti-gp120 RNA aptamer
HT Mufhandu1*, KB Alexandre2, ES Gray2, L Morris2, M Khati1
From AIDS Vaccine 2012
Boston, MA, USA. 9-12 September 2012
Background
Globally, HIV-1 subtype C is the most prevalent subtype,
yet most antiretroviral drugs are developed against subtype
B. UCLA1 RNA aptamer, which we previously showed
neutralizes HIV-1 subtype C Env-pseudotyped viruses was
examined for neutralization of subtype C primary isolates
in PBMC and monocyte-derived macrophages (MDM).
We also assessed the ability of subtype C to develop resis-
tance to UCLA1 inhibition by propagating the isolates in
increasing concentrations of the aptamer.
Methods
UCLA1 was tested against clinical isolates in PBMC (6 iso-
lates) and MDM (4 isolates) using a p24 antigen read-out.
Three viruses were grown in the presence of increasing
aptamer concentrations to select for resistance. The
viruses were passaged every 7 days up to 12 weeks in CD8
depleted PBMC. The gp160 was sequenced, analyzed and
compared with wildtype viruses.
Results
UCLA1 neutralized 67% and 75% of viruses tested in
PBMC and MDM, respectively. Overall, the aptamer neu-
tralized one X4 and six R5 tropic viruses with IC80 values
in the nanomolar range. Two viruses remained sensitive to
the aptamer even in the presence of 4- and 12-fold
increased UCLA1 concentrations. One isolate exhibited
resistance after 12 weeks of propagation tolerating 12-fold
the starting IC70. Fifty-eight amino acid changes and two
insertions along the gp160 were observed. The changes
observed within the V1/V2 and V3 loops confirmed our
previous data shown by truncation and single point muta-
tional analyses to confer resistance to UCLA1.
Conclusion
UCLA1 was able to neutralize infection of primary isolates
in PBMC and MDM without tropism restriction. The
extensive amino acid sequence changes associated with
UCLA1 resistance may indicate a high genetic barrier
needed for resistance to UCLA1. This was also suggested
by the low rate of resistance (only 1 of 3 isolates) observed
in the study suggesting that UCLA1 is a potential anti-
HIV-1 subtype C entry inhibitor drug.
Author details
1Council for Scientific and Industrial Research (CSIR), Pretoria, South Africa.
2National Institute for Communicable Diseases (NICD), Johannesburg, South
Africa.
Published: 13 September 2012
doi:10.1186/1742-4690-9-S2-P215
Cite this article as: Mufhandu et al.: HIV-1 subtype C primary isolates
exhibit high sensitivity to an anti-gp120 RNA aptamer. Retrovirology 2012
9(Suppl 2):P215.
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Mufhandu et al. Retrovirology 2012, 9(Suppl 2):P215
http://www.retrovirology.com/content/9/S2/P215
© 2012 Mufhandu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
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HIV-1 subtype C primary isolates exhibit high sensitivity to an anti-gp120 RNA aptamer

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HIV-1 subtype C primary isolates exhibit high sensitivity to an anti-gp120 RNA aptamer

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