JOURNAL ARTICLE

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
Proceedings of the National Academy of Sciences of the United States of America 2009 April 14, 106 (15): 6321-6
19336585
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-kappaB-independent manner, and isolated an alternatively spliced form of the transcription factor Ets-1, DeltaVII-Ets-1. DeltaVII-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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