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Open Access Highly Accessed Review

HIV-1 transcription and latency: an update

Carine Van Lint1*, Sophie Bouchat1 and Alessandro Marcello2*

Author Affiliations

1 Université Libre de Bruxelles (ULB), Service of Molecular Virology, Institute of Molecular Biology and Medicine, 12, Rue des Profs Jeener et Brachet, 6041, Gosselies, Belgium

2 The Laboratory of Molecular Virology, International Centre for Genetic Engineering and Biotechnology (ICGEB), 34149, Trieste, Italy

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Retrovirology 2013, 10:67  doi:10.1186/1742-4690-10-67

Published: 26 June 2013

Abstract

Combination antiretroviral therapy, despite being potent and life-prolonging, is not curative and does not eradicate HIV-1 infection since interruption of treatment inevitably results in a rapid rebound of viremia. Reactivation of latently infected cells harboring transcriptionally silent but replication-competent proviruses is a potential source of persistent residual viremia in cART-treated patients. Although multiple reservoirs may exist, the persistence of resting CD4+ T cells carrying a latent infection represents a major barrier to eradication. In this review, we will discuss the latest reports on the molecular mechanisms that may regulate HIV-1 latency at the transcriptional level, including transcriptional interference, the role of cellular factors, chromatin organization and epigenetic modifications, the viral Tat trans-activator and its cellular cofactors. Since latency mechanisms may also operate at the post-transcriptional level, we will consider inhibition of nuclear RNA export and inhibition of translation by microRNAs as potential barriers to HIV-1 gene expression. Finally, we will review the therapeutic approaches and clinical studies aimed at achieving either a sterilizing cure or a functional cure of HIV-1 infection, with a special emphasis on the most recent pharmacological strategies to reactivate the latent viruses and decrease the pool of viral reservoirs.

Keywords:
HIV-1; Transcription; Post-integration latency; Persistence; Chromatin; Pharmacological strategies; Reservoirs; Therapy; Cure