New tool to find latent HIV in human DNA discovered

A team of researchers led by Guillaume Filion –head of the Genome Architecture laboratory at the Center for Genomic Regulation (CRG)− in collaboration with researchers from Pompeu Fabra University (UPF) has developed technology to help understand the role of chromatin silencing in latent HIV response to drugs currently available. The results obtained with this technology have shed light on a fundamental issue that was previously unresolved and contribute new information on basic principles of gene regulation.

One of the difficulties in treating people infected with HIV is that, when the virus enters the genome of the infected cell, part of the virus becomes inactive, lying dormant so the immune system cannot detect it. The DNA of HIV is silenced by the chromatin (a complex made up of DNA and proteins that surrounds and condenses DNA to make chromosomes) of the host cell. So, even though the patient is being treated with one of the available forms of therapy, the latent HIV can reactivate at any time and begin the cycle of infection all over again. Many therapies available today try to reactivate latent HIV in order to eliminate the dormant virus from the population. So far, however, none of them have been successful.

The technology developed by researchers at the CRG and UPF, published in the journal Nature Structural and Molecular Biology, is called B-HIVE and has put a sort of barcode on a population of viruses, so each virus can be identified individually with the chromosome where it is located. They've created a map of where the virus is located and, by measuring its level of expression, have seen that latent-HIV reactivation therapies depend in part on their place in the human genome.

Using this new technology, researchers have shown that different drugs used to reactivate HIV affect different areas of the chromosome. This means that these drugs are more selective than was previously thought. “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,” adds enthusiastically Andreas Meyerhans, an HIV researcher co-authoring this paper and ICREA research professor in the UPF Department of Experimental and Health Sciences. But although results are encouraging, how these hopeful results benefits individuals infected with HIV is yet to be seen.

Related publication:

• Chen HC et al. “Position effects influence HIV latency reversal”. Nature Structural and Molecular Biology 2016 (November 21 2016) DOI: nsmb.3328