Viruses have played an important role in human evolution, and some have even become a permanent part of our DNA. The ENDo-HERPES project explores one such example — a herpesvirus called human herpesvirus 6 (HHV-6) — which has integrated its genetic material into human chromosomes and is now inherited by around 80 million people worldwide. This remarkable condition, known as inherited chromosomally integrated HHV-6 (iciHHV-6), means that the virus is present in every cell of the affected individual and can be passed on to future generations. Although HHV-6 is common and usually harmless, its reactivation from the integrated state has been linked to several severe diseases, including seizures, encephalitis, heart failure, and organ transplant rejection. Yet, we still know very little about how and why these reactivations occur, or how the integrated virus affects human health.
ENDo-HERPES seeks to answer these questions using cutting-edge genomic, molecular, and cellular technologies. The project will first determine which of the distinct groups of integrated viral genomes are still functional and capable of producing infectious virus. It will then identify where in human chromosomes the virus has integrated and how this process occurred. Finally, it will investigate how the presence of the viral genome influences host cells and whether age-related shortening of chromosome ends, called telomeres, can trigger the virus to reactivate. These studies combine advanced techniques such as CRISPR/Cas9 genome editing, long-read nanopore sequencing, and high-resolution imaging to uncover the intricate relationship between the virus and the human genome.
By revealing the biological mechanisms behind HHV-6 integration and reactivation, ENDo-HERPES will help clarify whether the virus merely coexists with us or actively contributes to disease. This knowledge will likely lead to new diagnostic tools to identify individuals at risk and guide the development of treatments that prevent or control virus reactivation. Beyond virology, the findings will provide insights into telomere biology, human evolution, and the long-term consequences of viral DNA embedded in our genome.
