The site of its latent infection is not yet known, but could be monocytes/macrophages. In normal healthy blood donors it was found that 0.8–1.0% had high viral loads most likely attributed to iHHV-6 integration in the germ-line. The prevalence of integrated iHHV-6 in hospitalized patients was higher, 2.9–3.3%. Human herpesvirus 6 congenital infection results primarily from chromosomally integrated virus which is passed through the germ-line. We, therefore, postulated that if the chromosomally integrated virus does replicate, women with CI-HHV-6 could have congenitally infected infants not only from germline passage of the chromosomally integrated virus, but also from transplacental passage of HHV-6. Future studies are required to determine the overall impact of the integrated virus whether it may have harmful effects on hospitalized patients and understand disease progression associated with iHHV-6. The full length genome of EBV infrequently integrates into random chromosome sites during latency.
The gammaherpesvirus Marek’s Disease Virus (MDV) frequently integrates into the telomere of chickens through telomeric repeats. Of the six shelterin proteins, TRF2 was shown to bind to the three nonamer EBV encoded TTAGGGTTA repeat within the origin of latent DNA replication (oriP) in cooperation with viral latency gene EBNA-1. It is hypothesized by the authors that the binding of telomere repeats encoded in the DR of HHV-6 by TRF2/TRF1 plays a role in telomere mediated integration by facilitating the localization of the viral genome to the telomere of chromosomes. It is suggested, that ORF U94 may function as a latency gene and possibly facilitate HHV-6A/HHV-6B specific integration into telomeres similar to its AAV-2 encoded rep68/78 counterpart. The integration of HHV-6 into chromosomes is not a dead end pathway; the virus is shown to reactivate from its latent integrated state and leads to infection of naïve cells resulting in cell death. It is proposed that integration of HHV-6 into the telomere of chromosomes occurs through homologous recombination. However, it remains unknown whether the viral latency gene ORF U94 and telomere binding proteins TRF1 and TRF2 do in fact play a role during the process of integration.
Furthermore, the physiological effect and impact on the stability of iHHV-6 has on the telomere remains unknown.