“Chromosomally integrated HHV-6” (ciHHV-6) is an inherited condition in which the complete HHV-6 genome is integrated into the telomere of every chromosome. The condition affects slightly less than 1% of the population in the US and UK, but appears to affect a greater percentage of patients than healthy controls. (Pellett 2012). The condition was found to increase the odds of developing angina (Gravel 2015) and may be over-represented in patients with encephalitis. Preliminary evidence suggests that some individuals may have a difficult time mounting an immune response against strains they encounter from others, resulting in persistent infection, cognitive dysfunction and fatigue (Pantry 2013, Montoya 2012).

The integrated virus can excise itself from the chromosome and activate under certain circumstances, such as immune deficiency (Endo 2014). Also ciHHV6 pregnant women can shed active virus which can be passed to their fetuses during pregnancy (Gravel 2013) with unknown consequences. Chromosomally integrated HHV-6 can be inherited from either parent, so families with one carrier (father or mother) have a 50% chance of passing the condition on to each child. Chromosomally integrated HHV-6 individuals will always have a very high viral load in whole blood testing—generally over 1 million copies per ml — but testing on plasma will be low or below the level of detection unless the individual is acutely ill. In countries where plasma testing is standard, the condition is often missed or mistaken for an active infection. Individuals with ciHHV-6 should be cautious about using drugs such as steroids or HDAC inhibitors, that are known to activate HHV-6.

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It is very easy to identify an individual with ciHHV6 using a quantitative PCR DNA test on whole blood, available at ViracorIBT or Coppe Laboratories in the US, and IKDT in Germany. HHV-6 DNA levels in unaffected individuals are less than 50 copies/ml in whole blood testing or undetectable. Only transplant patients with encephalitis or graft vs host disease (GVHD) or patients with drug-induced hypersensitivity syndrome (DIHS) have been reported to have DNA loads comparable to those found in patients with ciHHV-6, or over 500,000 copies per ml in whole blood. Confirmation of inherited ciHHV6 can be done by testing for HHV-6 PCR DNA in a hair follicle or nail clipping at Coppe Laboratories (only ciHHV6 individuals have HHV-6 DNA in these cells) or by requesting a digital droplet PCR (ddPCR) test from the clinical lab of the University of Washington. This test confirms that the patient has a 1:1 ratio of HHV-6 genomes to human cells.