Human herpesvirus-6A (HHV-6A) is rarer than HHV-6B in many infant populations. However, they are similarly prevalent as germline, chromosomally integrated genomes (ciHHV-6A/B). This integrated form affects 0.1-1 % of the human population, where potentially virus gene expression could be in every cell, although virus relationships and health effects are not clear. In a Czech/German patient cohort ciHHV-6A was more common and diverse than ciHHV-6B. Quantitative PCR, nucleotide sequencing and telomeric integration site amplification characterized ciHHV-6 in 44 German myocarditis/cardiomyopathy and Czech malignancy/inflammatory disease (MI) patients plus donors. Comparisons were made to sequences from global virus reference strains, and blood DNA from childhood-infections from Zambia (HHV-6A mainly) and Japan (HHV-6B). The MI cohort were 86 % (18/21) ciHHV-6A, the cardiac cohort 65 % (13/20) ciHHV-6B, suggesting different disease links. Reactivation was supported by findings of 1) recombination between ciHHV-6A and HHV-6B genes in 20 % (4/21) of the MI cohort; 2) expression in a patient subset, of early/late transcripts from the inflammatory mediator genes chemokine receptor U51 and chemokine U83, both identical to ciHHV-6A DNA sequences; and 3) superinfection shown by deep sequencing identifying minor virus-variants only in ciHHV-6A, which expressed transcripts, indicating virus infection reactivates latent ciHHV-6A. Half the MI cohort had more than two copies per cell, median 5.2, indicative of reactivation. Remarkably, the integrated genomes encoded the secreted-active form of virus chemokines, rare in virus from childhood-infections. This shows integrated virus genomes can contribute new human genes with links to inflammatory pathology and supports ciHHV-6A reactivation as a source for emergent infection.

• MeSH
• aktivace viru MeSH
• cytokiny analýza   MeSH
• infekce roseoloviry virologie   MeSH
• kohortové studie MeSH
• kojenec MeSH
• lidé MeSH
• lidské chromozomy virologie   MeSH
• lidský herpesvirus 6 genetika   MeSH
• molekulární sekvence - údaje MeSH
• sekvenční analýza DNA MeSH
• virové proteiny analýza   MeSH
• zárodečné buňky virologie   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Německo MeSH

Two patients with the characteristic high human herpesvirus 6 (HHV-6) DNA loads in peripheral blood caused by chromosomally integrated (CI) virus received a haematopoietic stem cell transplant (HSCT) from a donor without CI HHV-6. Both patients died in consequence of cytomegalovirus (CMV) pneumonitis. At autopsy, high amounts of CMV DNA were detected in lungs but at much lower levels in other organs. In contrast HHV-6 DNA was detected at high levels throughout the organs with the exception of donor-derived haematopoietic tissue. In individuals with chromosomal integration, HHV-6 DNA is found in every tissue of recipient origin indicating inheritance through the germ line.

• MeSH
• akutní lymfatická leukemie mortalita   terapie   virologie   MeSH
• akutní myeloidní leukemie mortalita   terapie   virologie   MeSH
• cytomegalovirové infekce mortalita   MeSH
• Cytomegalovirus izolace a purifikace   MeSH
• dítě MeSH
• DNA virů analýza   MeSH
• dospělí MeSH
• fatální výsledek MeSH
• financování organizované MeSH
• infekce roseoloviry genetika   virologie   MeSH
• integrace viru genetika   MeSH
• lidé MeSH
• lidské chromozomy virologie   MeSH
• lidský herpesvirus 6 genetika   MeSH
• plíce virologie   MeSH
• pneumonie mortalita   virologie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• transplantace hematopoetických kmenových buněk MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH