The prevalence of chromosomally integrated human herpesvirus 6 genomes in the blood of UK blood donors

Abstract

A lesser-recognized form of human herpesvirus 6 (HHV-6) persistence is integration of the viral genome in a host chromosome and high viral copy numbers in blood or sera are characteristic of this phenomenon. A cross-sectional study was performed to determine the frequency of high HHV-6 viral loads in whole blood (>6 log(10) copies/ml) in a population of blood donors in London, UK. Blood samples from 500 anonymized blood donors were collected from one donation center, DNA extracted, and quantitative realtime PCR used to measure viral load. Four samples (0.8%) were found to have high viral copy numbers of HHV-6 (median 6.7 log(10) copies/ml; range 6.5- 6.9 log(10) copies/ml). Cellular DNA was also quantitated using qRT-PCR for beta-globin. By comparing these two results, we calculated that there were between two and five copies of HHV-6 present per cell in these four donors. The median viral load detected in plasma from the four individuals was 3.8 log(10) copies/ml (range 3.5-4.0 log(10) copies/ml). All samples were HHV-6 variant B. In addition, a retrospective analysis of all diagnostic blood samples performed for HHV-6 in our center showed a prevalence of 2.9% of high viral loads characteristic of integration. In conclusion, high viral copy numbers of HHV-6, representing a population of viral integration, is detected in 0.8% of UK blood donors. The presence of high HHV-6 viral loads in healthy normal individuals reiterates the need to consider the confounding effect of HHV-6 viral integration in any laboratory diagnosis of HHV-6 infection.

Human herpes virus 6 infection is a hallmark of cord blood transplant in adults and may participate to delayed engraftment: a comparison with matched unrelated donors as stem cell source

“…39 Finally, two cases consistent with chromosomally integrated HHV6 were also observed, which is in accordance with the prevalence of 0.2-0.8% observed in the general population. 40,41 In conclusion, our results show that after allo-HSCT, the pattern of HHV6 infection is dependent on the source of SCs. A specific relationship is suggested between HHV6 infection and the use of CB cells but larger studies are still needed, especially to better define the role of immune reconstitution.…”

Human Herpesvirus 6 DNA Levels in Cerebrospinal Fluid Due to Primary Infection Differ from Those Due to Chromosomal Viral Integration and Have Implications for Diagnosis of Encephalitis

“…Although neither our survey of HHV-6 DNA in CSF nor those discussed above included normal controls, the prevalence in such controls due to viral integration should be between 0.7% (95% confidence limits, 0.2 to 2.1) and 1.5% (95% confidence limits, 0.7 to 2.8) as judged by our two separate reports of high level serum or plasma HHV-6 DNA, i.e., presumed chromosomal integration, in control populations (24,47). Further support for these estimates comes from the reported prevalences of between 0.9 to 1.6% for congenital HHV-6 infection (1, 9, 17), i.e., presumed chromosomal integration.…”

“…A serum HHV-6 DNA concentration of Ͼ3.5 log 10 copies/ml was defined as high based on the 95% confidence limits for the mean level found in individuals with persistent high levels of HHV-6 DNA (24,46,47).…”

Human herpesvirus-6 encephalitis after allogeneic hematopoietic cell transplantation: What we do and do not know

“…27 This condition, ciHHV-6, is considered to be present in ∼ 1% of the populations of the United States and United Kingdom. 28,29 Although ciHHV-6 can be induced to a state of viral replication both in vitro 27 and in vivo, 30,31 whether the integrated virus can reactivate and cause disease in the setting of allo-HCT is unknown. To date, only one case of a patient with ciHHV-6A and HHV-6A reactivation as a possible cause of HHV-6 encephalitis in the setting of allo-HCT has been reported.…”