Virology

Stochastic Reservoir

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Science  22 Nov 2013:
Vol. 342, Issue 6161, pp. 910
DOI: 10.1126/science.342.6161.910-c

A major challenge in attempting to eradicate HIV is the virus that remains latent (transcriptionally inactive) in infected cells; current pharmacological therapies focus on inhibiting various steps in the HIV life cycle. It has been thought that the reason latent viruses are inactive is either that they infected T cells that were transitioning to a resting state or that the viruses themselves were defective. The latent reservoir has been measured in the past by one of two methods: forcing all T cells to become active and then measuring viruses that have been induced to replicate (which could lead to underestimates, because not all proviruses have been induced) or identifying all integrated proviral DNA (which may include defective genomes that would never replicate). Ho et al. have gone further, by analyzing the viruses that remained inactive after T cell activation. Intact viral genomes were found in nearly 12% of the clones analyzed. When they synthesized a sample of the genomes and reconstructed these viruses, replication occurred with normal growth kinetics, and promoter function appeared normal. The reason for latency was not that the viruses had integrated into heterochromatin, whence transcription would be suppressed, nor had these noninduced viruses been silenced by CpG methylation. This makes the prospects for a sterilizing cure look somewhat farther away—the authors conclude that the latent reservoir may be as much as 60 times larger than previous estimates.

Cell 155, 540 (2013).

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