Technology Sheds Light on Clearing Latent HIV

Newly developed technology maps HIV inserts across the human genome.

New technology has been developed to discover the role chromatin silencing has in the response of latent HIV to available drugs.

This technology sheds light on HIV, revealing that the response of latent HIV to reactivation therapies depends partly on the integration site in the human genome, according to a study published in Natural Structural and Molecular Biology.

Current treatments try to attack latent HIV in order to clear the population of the virus, but none of the proposed therapies have proven effective curing infected patients.

In the current study, researchers developed the technology B-HIVE, which allowed them to map HIV inserts across the human genome and measure their expression levels.

“We barcoded a population of viruses with a genetic identifier,” said lead study author Guillaume Filion. “With the barcodes, we were able to link an individual virus to its chromosomal location. Also, we were able to measure their expression levels and showed that the response of HIV to reactivation therapies partly depends on the integration site in the human genome. For the first time, it shows the practical relevance of the chromatin context in the fight against HIV.”

By using the B-HIVE technology, the researchers demonstrated that different HIV drugs reactivate the virus from different locations within the chromosome, the study found. This indicates that the reactivation drugs are more selective than was previously believed.

“Having this technique in hand, we can now search for the best drug mix that can reactivate all the latent viruses that up to now were hiding from the antiretroviral drugs in use today and make them susceptible to destruction,” said first study author Heng-Chang Chen. “Our study suggests to orient future investigations towards the development of drugs with complementary targets. This is a big step forward and will definitely boost HIV cure research as well as our understanding of the dormant state of HIV called latency.”

The new genome-wide maps of HIV expression will provide further information into the basic principle of gene regulation and will be a useful resource for data analysts interest in clinical applications, the study noted.