Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 15, Pages 6321-6326Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0809536106
Keywords
antiretroviral therapy; Delta VII-Ets-1; expression cloning; long terminal repeat; viral reservoir
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Funding
- National Institutes of Health [AI043222]
- Rita Allen Foundation Scholar
- Sidney Kimmel Foundation for Cancer Research
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HIV-1 latency in resting CD4(+) T cells represents a major barrier to virus eradication in patients on highly active antiretroviral therapy (HAART). Eliminating the latent HIV-1 reservoir may require the reactivation of viral gene expression in latently infected cells. Most approaches for reactivating latent HIV-1 require nonspecific T cell activation, which has potential toxicity. To identify factors for reactivating latent HIV-1 without inducing global T cell activation, we performed a previously undescribed unbiased screen for genes that could activate transcription from the HIV-1 LTR in an NF-kappa B-independent manner, and isolated an alternatively spliced form of the transcription factor Ets-1, Delta VII-Ets-1. Delta VII-Ets-1 activated HIV-1 transcription through 2 conserved regions in the LTR, and reactivated latent HIV-1 in cells from patients on HAART without causing significant T cell activation. Our results highlight the therapeutic potential of cellular factors for the reactivation of latent HIV-1 and provide an efficient approach for their identification.
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