Viral 'sleeper agents' in human genomes could make HIV even harder to cure than expected.

Dormant HIV sequences called proviruses embed themselves in the DNA of immune-system cells, thwarting efforts to eliminate HIV infection. However, in laboratory tests, less than 1% of proviruses could be reactivated — the rest were thought to be so mutated that they are unable to awaken and spread.

Now, Robert Siliciano of Johns Hopkins University in Baltimore, Maryland, and his colleagues show that in people who have been treated for HIV, the proportion of potentially active proviruses is higher than assumed. The researchers sequenced DNA of 213 inactive proviruses from people with HIV and found that around 12% of proviruses still had intact genomes. That makes the reservoir of latent virus some 60 times larger than previous estimates.

Cell 155, 540–551 (2013)