22/06/2016 - 12:00 - Auditori PRBB

HIV, chromatin and 3D

Scientific sessions, CRG Group Leader Seminars

Guillaume Filion

Genome Architecture Group, Gene Regulation, Stem Cells and Cancer Programme, CRG

Guillaume Filion started his doctoral research on epigenetics at the Curie Institute in 2004, under the supervision of Dr. Pierre-Antoine Defossez. In 2008, he moved to the Netherlands, as a post-doc in the laboratory of Dr. Bas van Steensel. In 2012, he obtained a junior group leader position at the CRG.

To complete the infection cycle, HIV needs to be inserted in the genome of its host cell. This step is critical, as it allows the virus to become latent and to establish a a reservoir of infected cells without any sign of infection. For this reason, patients infected with HIV cannot interrupt the anti-retroviral therapy at any moment, otherwise the virus rebounds and all the symptoms of the infection quickly reappear. How and why HIV goes latent remains mostly speculative. Surprisingly little attention has been brought to the hypothesis that HIV may be silenced by the chromatin of the host. To test this idea, we have developed a technology called B-HIVE (Barcoded HIV Ensembles) in which we tag viral genomes with a barcode to follow their insertion and expression in the host cell. Using B-HIVE, we have discovered that HIV latency depends on the insertion site. Insertions far from human enhancers are more likely to be latent. In addition, we have used B-HIVE to test several latency reversal drugs and have discovered that their typical targets have distinct insertion sites. Our results thus suggest that the chromatin of the host plays a key role in the fate of the HIV infection and in the perspective of treatment.