Inherited Chromosomally Integrated Human Herpesvirus 6 Demonstrates Tissue-Specific RNA Expression In Vivo That Correlates with an Increased Antibody Immune Response
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Abstract
HHV-6A and -6B are human herpesviruses that have the unique property of being able to integrate into the telomeric regions of human chromosomes. Approximately 1% of the world’s population carries integrated HHV-6A/B genome in every cell of their body. Whether viral genes are transcriptionally active in these individuals is unclear. By taking advantage of a unique tissue-specific gene expression data set, we showed that the majority of tissues from iciHHV-6 individuals do not show HHV-6 gene expression. Brain and testes showed the highest tissue-specific expression of HHV-6 genes in two separate data sets. Two HHV-6 genes, U90 (immediate early 1 protein) and U100 (glycoproteins Q1 and Q2), were found to be selectively and consistently expressed across several human tissues. Expression of U90 translates into an increase in antigen-specific antibody response in iciHHV-6A/B + subjects relative to controls. Future studies will be needed to determine the mechanism of gene expression, the effects of these genes on human gene transcription networks, and the pathophysiological impact of having increased viral protein expression in tissue in conjunction with increased antigen-specific antibody production.
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In an immunocompetent individual, iciHHV-6 is the most frequent reason for the detection of HHV-6 DNA in the CSF.
“in an immunocompetent individual, iciHHV-6 is the most frequent reason for the detection of HHV-6 DNA in the CSF.”
From Meningoencephalitis in a background of inherited chromosomic integration of HHV-6 and CMV infection in an immunocompetent adult, which one is the culprit? (2025) · cites this paper as [14]
The Introduction (page unavailable) says HHV-6 DNA is always present in the cells of people with iciHHV-6, which can confound DNA-based tests for active infection. It does not address CSF testing in immunocompetent people or establish that iciHHV-6 is the most frequent reason for a positive CSF result. (LLM, conf=0.79)
Experimental — accuracy not yet measuredMost HHV-6-positive CSF samples indirectly reflect chromosomal integration and are considered clinically irrelevant.
“Most HHV-6-positive CSF samples indirectly reflect chromosomal integration and are considered to be clinically irrelevant [14].”
From Meningoencephalitis in a background of inherited chromosomic integration of HHV-6 and CMV infection in an immunocompetent adult, which one is the culprit? (2025) · cites this paper as [14]
The Introduction (page unavailable) says inherited chromosomal integration can confound DNA-based PCR diagnosis because HHV-6 DNA is present in patients’ cells. It does not establish that most HHV-6-positive CSF samples result from integration or that those findings are clinically irrelevant. (LLM, conf=0.84)
Experimental — accuracy not yet measured
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- [15]Peddu V, Dubuc I, Gravel A, Xie H, Huang M-L, Tenenbaum D, Jerome KR, Tardif J-C, Dubé M-P, Flamand L, Greninger AL 2019 Inherited chromosomally integrated human herpesvirus 6 demonstrates tissue-specific RNA expression in vivo that correlates with an increased antibody immune response. bioRxiv 10.1101/741025. PMC6912112 31597766 · DOI
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- Authors
- Peddu, V., Dubuc, I., Gravel, A., Xie, H., Huang, M.-L., Tenenbaum, D., Jerome, K. R., Tardif, J.-C., Dubé, M.-P., Flamand, L., & Greninger, A. L.
- Affiliations
- University of Washington (US)
- Université Laval (CA)
- Fred Hutch Cancer Center (US)
- Montreal Heart Institute (CA)
- National Institutes of Health (US)
- ORCID
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2019-12-12
- Volume
- 94
- Issue
- 1
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC6912112
- OpenAlex
- W2979639930
- Cited by
- 39
- References
- 38
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 8 · 2019: 2
- FWCI
- 4.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Virology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Heart and Stroke Foundation of Canada
- Institut de Cardiologie de Montréal
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Keywords
- human herpesvirus 6, HHV-6A, HHV-6B, chromosomal integration, tissue-specific gene expression, immediate-early proteins, antigen-specific antibody response, viral transcription, brain, testis
- MeSH terms
- Whole Genome Sequencing, Adrenal Glands, Aged, Antibodies, Viral, Brain, Chromosomes, Human, Cytomegalovirus, Herpesvirus 4, Human, Esophagus, Female, Humans, Male, Middle Aged, Organ Specificity, Orthomyxoviridae, Phylogeny, RNA, Viral, Testis, Cohort Studies, Herpesvirus 6, Human, Virus Integration, Roseolovirus Infections, Inheritance Patterns
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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