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J Virol. 2010 Jun;84(12):5958-74. doi: 10.1128/JVI.00161-10. Epub 2010 Mar 31.

Combinatorial latency reactivation for HIV-1 subtypes and variants.

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1
Department of Chemical Engineering and Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, USA.

Abstract

The eradication of HIV-1 will likely require novel clinical approaches to purge the reservoir of latently infected cells from a patient. We hypothesize that this therapy should target a wide range of latent integration sites, act effectively against viral variants that have acquired mutations in their promoter regions, and function across multiple HIV-1 subtypes. By using primary CD4(+) and Jurkat cell-based in vitro HIV-1 latency models, we observe that single-agent latency reactivation therapy is ineffective against most HIV-1 subtypes. However, we demonstrate that the combination of two clinically promising drugs-namely, prostratin and suberoylanilide hydroxamic acid (SAHA)-overcomes the limitations of single-agent approaches and can act synergistically for many HIV-1 subtypes, including A, B, C, D, and F. Finally, by identifying the proviral integration position of latent Jurkat cell clones, we demonstrate that this drug combination does not significantly enhance the expression of endogenous genes nearest to the proviral integration site, indicating that its effects may be selective.

PMID:
20357084
PMCID:
PMC2876650
DOI:
10.1128/JVI.00161-10
[Indexed for MEDLINE]
Free PMC Article
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