Inducible HIV RNA transcription assays to measure HIV persistence: pros and cons of a compromise - PubMed (original) (raw)

Review

Inducible HIV RNA transcription assays to measure HIV persistence: pros and cons of a compromise

Johann Plantin et al. Retrovirology. 2018.

Abstract

With the increasing number of therapeutic strategies tested in humans to reduce the size of the latent reservoir, the development of a robust, precise and clinical trial scalable assay that measures the frequency of infected cells carrying inducible replication-competent HIV is urgently needed. The size of the pool of cells carrying replication-competent HIV is largely overestimated by DNA assays, as a result of a large proportion of defective viruses, and underestimated by co-culture outgrowth assays. New culture methods that measure the inducible HIV reservoir have been developed during the past few years. In these induction assays, CD4+ T cells from virally suppressed individuals are activated and HIV RNA is measured in cell extracts or cell supernatants. In this review, we summarize the principle and outcomes of these assays and discuss the potential of these methods in the evaluation of HIV eradication strategies.

Keywords: HIV reservoir; HIV transcription; Induced RNA.

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Figures

Fig. 1

Fig. 1

Transcriptional profiles of proviruses after stimulation. a A severe defect in the HIV genomes can completely abrogate its ability to produce viral transcripts after induction. b Some proviruses can produce short unspliced viral transcripts (usRNA) upon activation, but those may not undergo splicing, preventing the generation of multiply-spliced transcripts (msRNA). c, d Intact proviruses can be fully latent (c) or partially latent (leaky latency, d) After stimulation, msRNA are produced leading to the nuclear export of the full-length viral transcripts that results in the production of viral particles. Colour coded (+) and (−) symbols represent the presence or the absence, respectively of the molecular forms of HIV (DNA [red], usRNA [green], msRNA [orange] or cf-RNA [turquoise]) indicated at the bottom of the figure

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