A comprehensive study of DNA and RNA-Seq data demonstrated in vivo gene expression in many iciHHV-6 tissues, with strong expression of U90 encoding the IE-1 protein and matching elevated antibody response in iciHHV-6 individuals compared to controls. More viral RNA was expressed in the brain tissue of iciHHV-6A brains than in those with iciHHV-6B.
Vikas Peddu in Alex Greninger’s lab at University of Washington looked at DNA and RNA-Seq in ciHHV-6 individuals mined using data from 650 records in the Genotype-Tissue Expression (GTEx) project. He found U90 (the IE-1A transactivator) and U100 (envelope glycoprotein) had the highest level of expression in both ciHHV-6A and ciHHV-6B individuals.
Alex Greninger and Vikas Peddu from the Greninger Lab, University of Washington Medicine, Clinical Virology
Theorizing that the increased antigen burden in ciHHV-6 individuals might also increase antibody levels to HHV-6, Greninger then teamed up with Louis Flamand at University Laval in Quebec City, who screened 15,498 heart disease patients from the Montreal Heart Institute biobank, to identify 85 ciHHV-6 patients.
About a third of iciHHV-6 individuals had 25X higher antibody titers to HHV-6 immediate early (IE-1A) compared to controls. Mean antibody responses to ciHHV-6 1E-1B were 13X higher in ciHHV-6 individuals than controls.
Individuals with iciHHV-6 had 5-fold higher CMV pp150 antibodies; that ratio was statistically significant for iciHHV-6A. Individuals with iciHHV-6A also had higher levels of TNF alpha than iciHHV-6B individuals or controls.
A previous study demonstrated that iciHHV-6 individuals could reactivate with their inherited strains, with pathological effect (Endo 2014). This new study sheds light on the biological consequences of low level gene transcription in iciHHV-6 individuals.
Louis Flamand, Annie Gravel and Isabelle Dubuc, CHU de Quebec, University Laval
Of interest, there was a high percentage of ciHHV-6A patients in the Montreal Heart institute cohort, at 54% of the 85 identified. Most studies, such as the previous prevalence study done in Canada (Gravel 2015) identified more iciHHV-6B than iciHHV-6A patients.
Read the full paper: Peddu 2019
| Studies | # | Ici # | Ici % | iciHHV-6A | iciHHV-6B |
| CARTaGENE | 19,597 | 113 | .58% | 41% | 59% |
| Montreal Heart Institute | 15,498 | 85 | .55% | 54% | 46% |
| Genotype-Tissue Expression project | 650 | 6 | .92% | 33% | 67% |
Antibodies to HHV-6 IE1A (immediate early) antibodies were significantly elevated in iciHHV-6A/B individuals compared to antibodies against an HHV-6 glycoprotein U72