Fetal inheritance of chromosomally integrated human herpesvirus 6 predisposes the mother to pre-eclampsia
| Autor: | Ulla Sovio, Andrew M. Sharkey, Christian Delles, Julian Parkhill, Susanne Lager, Sharon J. Peacock, D. Stephen Charnock-Jones, Justyna Dopierala, Marcus C. de Goffau, Francesca Gaccioli, Gordon C. S. Smith, Sungsam Gong, Judith Breuer, Cristina Venturini, Ashley Moffett, Emma Cook, Wai K. Lee |
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| Přispěvatelé: | Lager, Susanne [0000-0003-3556-065X], Sovio, Ulla [0000-0002-0799-1105], Gong, Sungsam [0000-0001-5796-4423], Cook, Emma [0000-0002-6142-4443], Delles, Christian [0000-0003-2238-2612], Breuer, Judith [0000-0001-8246-0534], Parkhill, Julian [0000-0002-7069-5958], Peacock, Sharon J [0000-0002-1718-2782], Charnock-Jones, D Stephen [0000-0002-2936-4890], Smith, Gordon CS [0000-0003-2124-0997], Apollo - University of Cambridge Repository, Experimental Vascular Medicine, ACS - Diabetes & metabolism |
| Rok vydání: | 2020 |
| Předmět: |
Microbiology (medical)
Male Herpesvirus 6 Human Virus Integration Immunology Population Physiology Roseolovirus Infections Applied Microbiology and Biotechnology Microbiology Polymorphism Single Nucleotide 03 medical and health sciences Pre-Eclampsia Pregnancy Placenta Genetics medicine Humans education 030304 developmental biology 0303 health sciences education.field_of_study Fetus Eclampsia biology 030306 microbiology business.industry Case-control study Infant Newborn Infant Cell Biology Odds ratio Sequence Analysis DNA medicine.disease biology.organism_classification medicine.anatomical_structure Case-Control Studies DNA Viral RNA Viral Human herpesvirus 6 Female Disease Susceptibility Maternal Inheritance business |
| Zdroj: | Nature microbiology, 5(7), 901-908. Nature Publishing Group |
| ISSN: | 2058-5276 |
| Popis: | Pre-eclampsia (typically characterized by new-onset hypertension and proteinuria in the second half of pregnancy) represents a major determinant of the global burden of disease1,2. Its pathophysiology involves placental dysfunction, but the mechanism is unclear. Viral infection can cause organ dysfunction, but its role in placentally related disorders of human pregnancy is unknown3. We addressed this using RNA sequencing metagenomics4–6 of placental samples from normal and complicated pregnancies. Here, we show that human herpesvirus 6 (HHV-6, A or B) RNA was detected in 6.1% of cases of pre-eclampsia and 2.2% of other pregnancies. Fetal genotyping demonstrated that 70% of samples with HHV-6 RNA in the placenta exhibited inherited, chromosomally integrated HHV-6 (iciHHV-6). We genotyped 467 pre-eclampsia cases and 3,854 controls and found an excess of iciHHV-6 in the cases (odds ratio of 2.8, 95% confidence intervals of 1.4–5.6, P = 0.008). We validated this finding by comparing iciHHV-6 in a further 740 cases with controls from large-scale population studies (odds ratio of 2.5, 95% confidence intervals of 1.4–4.4, P = 0.0013). We conclude that iciHHV-6 results in the transcription of viral RNA in the human placenta and predisposes the mother to pre-eclampsia. Here, using RNA sequencing and data from several cohorts, the authors find an association of the presence of inherited, chromosomally integrated human herpesvirus 6 in the placenta with a clinical diagnosis of pre-eclampsia in the mother. |
| Databáze: | OpenAIRE |
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