Chromosomally integrated HHV-6: impact on virus, cell and organismal biology

•HHV-6A and HHV-6B integrate their genome into the telomeres of host chromosomes.•Genomes of HHV-6A, HHV-6B and other herpesviruses contain telomeric sequences (TTAGGG).•HHV-6A and HHV-6B can integrate in germ cells and are vertically transmitted.•TMR of Marek's disease virus (MDV) facilitates integration into host telomeres.•The integrated HHV-6 genome can be mobilized, allowing efficient reactivation. HHV-6 integrates its genome into telomeres of human chromosomes. Integration can occur in somatic cells or gametes, the latter leading to individuals harboring the HHV-6 genome in every cell. This condition is transmitted to descendants and referred to as inherited chromosomally integrated human herpesvirus 6 (iciHHV-6). Although integration can occur in different chromosomes, it invariably takes place in the telomere region. This integration mechanism represents a way to maintain the virus genome during latency, which is so far unique amongst human herpesviruses. Recent work provides evidence that the integrated HHV-6 genome can be mobilized from the host chromosome, resulting in the onset of disease. Details on required structural determinants, putative integration mechanisms and biological and medical consequences of iciHHV-6 are discussed.