Three-dimensional model of the retroviral intasome and chemical structures of some of the clinical HIV-1 integrase inhibitors studied in the lab

Peter Cherepanov : Chromatin structure and mobile DNA Laboratory

We want to understand how retroviruses infect cells and integrate their genetic material into host cell DNA, with the aim of improving treatment for HIV and gene therapy.

There are many different types of viruses that can infect human cells. Some, like the common cold virus, simply multiply inside an infected cell and then burst out to infect new hosts. But retroviruses, such as human immunodeficiency virus (HIV), insert their genetic material into the DNA of a host cell and can remain there, dormant and undetected by the immune system for very long time. It is this unique property that allows retroviruses to establish life-long persistent infections.

Our research is mostly directed at investigating exactly how retroviruses integrate their DNA into the host genome. The main techniques we use are X-ray crystallography and cryo-electron microscopy, which allow us to figure out the precise three-dimensional structures of the biological molecules that make up a retrovirus, as well as the molecular machinery inside human cells that enables it to copy its genes and settle into the host DNA.

Not only is our work revealing potential targets for the development of new drugs to treat HIV, we can also harness retroviruses for human health. Because they are so efficient at integrating into the host’s genome, retroviruses are used as vehicles to deliver therapeutic genes, such as genetically modified immune cells for treating cancer (known as CAR-T cells). The precise understanding of how retroviruses integrate will allow the development of safer gene therapy vectors to treat genetic diseases and cancer in the future.