Endogenous viruses present in the human genome control physiological processes, modulate aging, and can cause disease. “What is particularly interesting for us is that a specific herpesvirus has entered the human germ line by integrating its genome into the telomeres – the protective caps at the ends of chromosomes – of germ cells,” explains Kaufer. About eighty million people now carry this heritable, chromosomally integrated human herpesvirus 6 (iciHHV-6). The virus can be reactivated from its integrated state, which is associated with various diseases such as encephalitis, chronic heart failure, and transplant rejection.

“We recently analyzed iciHHV-6 viral genomes in hundreds of individuals. The data revealed that the current endogenous viral sequences are highly diverse, originating from dozens of independent integration events, and that they were inherited over generations,” adds Kaufer. However, Kaufer notes that there are critical gaps in knowledge about the functionality of iciHHV-6 genomes in terms of their viral replication, gene expression, and latency. The team will investigate the effects of the virus on the host cell, as well as the role of telomere shortening, which occurs during aging, in the reactivation of the virus.

The aim of the “ENDo-Herpes” research project is to close these gaps with the help of innovative technologies. This will also lay the foundations for answering the question of whether certain diseases are merely associated with iciHHV-6 or if they are in fact caused by the virus. Specifically, Kaufer and his team want to identify which iciHHV-6 genomes are still functional and whether they contribute to disease development. The integration sites of iciHHV-6 in the telomere region will also be determined, and the integration and reactivation process will be analyzed at the DNA level.

“The ‘ENDo-Herpes’ project will utilize state-of-the-art technologies and explore new approaches, particularly in terms of investigating the integration sites of endogenous virus genomes and the mechanisms that facilitate integration and reactivation. Overall, we will shed light on the life cycle and impact of this endogenous herpesvirus that presents in about one percent of the human population” Kaufer says.

Benedikt Kaufer has been director of the Institute of Virology at Freie Universität Berlin since 2020. He has also held a Lichtenberg Professorship at the university since 2017. Prior to this he was junior professor of molecular tumor virology at Freie Universität Berlin. He completed his undergraduate studies in molecular biotechnology at the Technical University of Munich and earned his PhD at Cornell University in New York (USA).

Picture available for download