Isolation of a cellular factor that can reactivate latent HIV-1 without T cell activation

Hung Chih Yang, Lin Shen, Robert F. Siliciano, Joel L. Pomerantz

Research output: Contribution to journalArticlepeer-review

Abstract

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-κB-independent manner, and isolated an alternatively spliced form of the transcription factor Ets-1, δVII-Ets-1. δVII-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.

Original languageEnglish (US)
Pages (from-to)6321-6326
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number15
DOIs
StatePublished - Apr 14 2009

Keywords

  • Antiretroviral therapy
  • Expression cloning
  • Long terminal repeat
  • Viral reservoir
  • δVII-Ets-1

ASJC Scopus subject areas

  • General

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