Possible Chromosomal and Germline Integration of Human Herpesvirus 7 (HHV-7).

Human herpesvirus 7 (HHV-7) is a betaherpesvirus and is phylogenetically related to both HHV-6A and HHV-6B. The presence of telomeric repeat sequences at both end of its genome should make it equally likely to integrate into human telomere as HHV-6. However, numerous studies have failed to detect germline integration of HHV-7 suggesting an important difference between the HHV-6A/-6B and HHV-7 genomes. In search of possible germline integrated HHV-7, we developed a sensitive and quantitative real time PCR assay and discovered that primers designed against some parts of HHV-7 genome can frequently miss HHV-7 positive clinical samples even though they work efficiently in cell culture derived HHV-7 positive materials. Using a primer pair against U90 ORF of HHV-7, we identified a possible case of germline integration of HHV-7 with one copy of viral genome per cell in both peripheral blood cell and hair follicles. Chromosomal integration of HHV-7 in these individuals was confirmed by FISH analysis. Germline integration of HHV-7 was further confirmed by detection of ~2.6 copies of HHV-7 in hair follicles of one of the parents. Our results shed light on complex nature of HHV-7 genome in human derived materials in comparison to cell culture-derived materials and ask for stringent criteria for selection of primers for epidemiological HHV-7 studies.