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human herpesvirus type 6; roseolovirus (HHV-6)

Classification: - apparently subtypes A & B [3] Epidemiology: - ~1% of humans have inherited the genomes of HHV-6 (HHV-6A & HHV-6B) Pathology: - virus latent in T-cells - subtype A (HHV-6A) may play a role in unexplained female infertility [3] - fetal inheritance of chromosomally integrated human herpesvirus 6 predisposes mother to pre-eclampsia [6] - HHV6A may affect metabolism of beta-amyloid precursor protein in brain [5] - HHV-6A/HHV-6B increases risk for systemic lupus erythematosus & pulmonary alveolar proteinosis disease activity [7] - HHV-6A/HHV-6B increases risk for angina pectoris [7,8] Clinical manifestations: - mononucleosis-like syndrome - 6th disease in children - may affect various organs in tranplant patients - menigoencephalitis in a stem-cell transplant patient [4] (case report) Laboratory: - Herpesvirus type 6 serology - Herpesvirus type 6 DNA - see ARUP consult [2]

General

herpesviridae

Properties

KINGDOM: virus GENOME-TYPE: deoxyribonucleic acid (DNA) DOUBLE-STRANDED GENOME-SIZE: 120-200 kB ENVELOPE: PRESENT CAPSID-SYMMETRY: ICOSAHEDRAL

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 11, 17, 18. American College of Physicians, Philadelphia 1998, 2015, 2018
  2. ARUP Consult: Herpesvirus 6 - HHV6 The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/human-herpesvirus-6
  3. Marci R, Gentili V, Bortolotti D et al Presence of HHV-6A in Endometrial Epithelial Cells from Women with Primary Unexplained Infertility. PLoS One. 2016 Jul 1;11(7):e0158304. eCollection 2016. PMID: 27367597 Free PMC Article
  4. El-Jawahri AR, Schaefer PW, El Khoury JB, Martinez-Lage M. Case 5-2018: A 63-Year-Old Man with Confusion after Stem-Cell Transplantation. N Engl J Med 2018; 378:659-669 PMID: 29443669 http://www.nejm.org/doi/full/10.1056/NEJMcpc1707556
  5. Readhead B, Haure-Mirande JV, Funk CC et al Multiscale Analysis of Independent Alzheimer's Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus. Neuron. June 2018. PMID: 29937276 https://www.cell.com/neuron/fulltext/S0896-6273(18)30421-5
  6. Gaccioli F, Lager S, de Goffau MC et al. Fetal inheritance of chromosomally integrated human herpesvirus 6 predisposes the mother to pre-eclampsia. Nat Microbiol 2020 May 4 PMID: 32367053 https://www.nature.com/articles/s41564-020-0711-3
  7. Sasa N et al. Blood DNA virome associates with autoimmune diseases and COVID-19. Nat Genet 2025 Jan; 57:65. PMID: 39753770 PMCID: PMC11735405
  8. Wood ML et al. Inherited chromosomally integrated human herpesvirus 6: Regional variation in prevalence, association with angina, and identification of ancestral viral lineages in two large UK studies. J Virol 2025 Jul 22; 99:e0216024 PMID: 40470957 PMCID: PMC12282103 https://journals.asm.org/doi/10.1128/jvi.02160-24 - Gravel A, Dubuc I, Morissette G, Sedlak RH, Jerome KR, Flamand L. Inherited chromosomally integrated human herpesvirus 6 as a predisposing risk factor for the development of angina pectoris. Proc Natl Acad Sci U S A. 2015 Jun 30;112(26):8058-63. PMID: 26080419 PMCID: PMC4491735 Free PMC article. https://www.pnas.org/doi/full/10.1073/pnas.1502741112