Human herpesvirus 7 integrates into host telomeres via its telomeric repeat arrays

Human herpesvirus 7 (HHV-7) is a ubiquitous betaherpesvirus and a causative agent of roseola infantum. HHV-7 harbors telomeric repeat arrays (TMR) identical to human telomeres at the ends of its genome. While similar repeats contribute to human herpesvirus 6 (HHV-6) integration into host telomeres, HHV-7 integration and the role of the TMR remained elusive. Using fluorescence in situ hybridization and nanopore sequencing, we demonstrate that HHV-7 efficiently integrates into host telomeres in persistently infected cells. To determine the role of the TMR in the virus life cycle, we generated the first HHV-7 reverse genetic system and mutants lacking the TMR. These mutants revealed that the TMR are dispensable for HHV-7 replication, but play a crucial role in the integration process and genome maintenance in persistently infected cells. This study provides a reverse genetic system for HHV-7, and offers important insights into the biology of this ubiquitous human pathogen.