The Splice of Life: Does RNA Processing Have a Role in HIV-1 Persistence?

Abstract

Antiretroviral therapy (ART) suppresses HIV-1 replication but does not eradicate the virus. Persistence of HIV-1 latent reservoirs in ART-treated individuals is considered the main obstacle to achieving an HIV-1 cure. However, these HIV-1 reservoirs are not transcriptionally silent, and viral transcripts can be detected in most ART-treated individuals. HIV-1 latency is regulated at the transcriptional and at multiple post-transcriptional levels. Here, we review recent insights into the possible contribution of viral RNA processing to the persistence of HIV-1 reservoirs, and discuss the clinical implications of persistence of viral RNA species in ART-treated individuals.

Keywords: HIV-1 latency; HIV-1 persistence; HIV-1 reservoir; RNA processing; splicing.

Figure 1

A simplified schematic representation of HIV-1 splicing. Upper panels: HIV-1 open reading frames. Positions of donor (D1–D5) and acceptor (A1–A8) splice sites and of the Rev response element (RRE) are shown. Lower panels: the main representatives of unspliced, incompletely spliced, and multiply spliced HIV-1 RNA classes. Gag and Pol proteins are expressed from the 9 kb unspliced RNA. The other HIV-1 proteins are expressed from either incompletely (Vif, Vpr, Env, and Vpu) or multiply (Tat, Rev, and Nef) spliced RNAs. RRE is present in unspliced and incompletely spliced RNAs but not in multiply spliced RNAs. Exons are shown by bars and introns by dashed lines. (Figure adapted from [24]; reproduced, with permission, from Elsevier).