Reactivate Latent HIV

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PNAS
Proceedings of the National Academy of Sciences of the United States of America
   
Isolation of a cellular factor that can reactivate latent HIV-1 without T cell activation
Hung-Chih Yanga, Lin Shena, Robert F. Silicianoa,b and Joel L. Pomerantzc,d,1
+Author Affiliations
 
Edited by Diane E. Griffin, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, and approved February 6, 2009 (received for review September 23, 2008)

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.


LINK:

http://www.pnas.org/content/106/15/6321.short