{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:03:01Z","timestamp":1792587781179,"version":"4.5.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T00:00:00Z","timestamp":1601251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP 19K17346"],"award-info":[{"award-number":["JP 19K17346"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Human herpesvirus 6 (HHV-6) can be genetically transmitted from parent to child as inherited chromosomally integrated HHV-6 (iciHHV-6). HHV-6 reactivation occurs in pregnant women with iciHHV-6. We found no sex differences in the frequency of index cases with iciHHV-6 but inheritance from the father was more common. We evaluated the association between iciHHV-6 status and spontaneous abortion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>iciHHV-6 was confirmed by high viral DNA copy numbers in whole blood and somatic cells. The origin of integrated viral genome, paternal or maternal, was examined using the same method. The pregnancy history of 23 mothers in families with iciHHV-6 and 285 mothers in families without iciHHV-6 was abstracted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 23 iciHHV-6 index cases, 8 mothers and 15 fathers had iciHHV-6. Spontaneous abortion rates in mothers with and mothers without\/fathers with iciHHV-6 and mothers in families without iciHHV-6 were 27.6%, 10.3%, and 14.8%, respectively (P\u2005=\u2005.012). Mothers with iciHHV-6 (odds ratio [OR], 6.41; 95% confidence interval [CI], 1.10\u201337.4) and maternal age at the most recent pregnancy \u226540 years (OR, 3.91; 95% CI, 1.30\u201311.8) were associated with 2 or more spontaneous abortions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Mothers with iciHHV-6 is a risk factor for spontaneous abortion.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiaa606","type":"journal-article","created":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T15:11:21Z","timestamp":1601046681000},"page":"1717-1723","source":"Crossref","is-referenced-by-count":38,"title":["Inherited Chromosomally Integrated Human Herpesvirus 6 Is a Risk Factor for Spontaneous Abortion"],"prefix":"10.1093","volume":"223","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2847-3374","authenticated-orcid":false,"given":"Hiroki","family":"Miura","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Kawamura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamae","family":"Ohye","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Graduate School of Health Sciences, Fujita Health University, Toyoake, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumihiko","family":"Hattori","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Kozawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Ihira","sequence":"additional","affiliation":[{"name":"Faculty of Clinical Engineering, Fujita Health University School of Health Sciences, Toyoake, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Yatsuya","sequence":"additional","affiliation":[{"name":"Department of Public Health, Fujita Health University School of Medicine, Toyoake, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruki","family":"Nishizawa","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Fujita Health University School of Medicine, Toyoake, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Kurahashi","sequence":"additional","affiliation":[{"name":"Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsushi","family":"Yoshikawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,9,28]]},"reference":[{"key":"2021052811195304800_CIT0001","doi-asserted-by":"crossref","first-page":"8040","DOI":"10.1128\/JVI.73.10.8040-8052.1999","article-title":"Human herpesvirus 6B genome sequence: coding content and comparison with human herpesvirus 6A","volume":"73","author":"Dominguez","year":"1999","journal-title":"J Virol"},{"key":"2021052811195304800_CIT0002","doi-asserted-by":"crossref","first-page":"8053","DOI":"10.1128\/JVI.73.10.8053-8063.1999","article-title":"Comparison of the complete DNA sequences of human herpesvirus 6 variants A and B","volume":"73","author":"Isegawa","year":"1999","journal-title":"J Virol"},{"key":"2021052811195304800_CIT0003","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/S0140-6736(88)91893-4","article-title":"Identification of human herpesvirus-6 as a causal agent for exanthem subitum","volume":"1","author":"Yamanishi","year":"1988","journal-title":"Lancet"},{"key":"2021052811195304800_CIT0004","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/S0022-3476(89)80078-2","article-title":"Human herpesvirus type 6 infection (exanthem subitum) without fever","volume":"115","author":"Asano","year":"1989","journal-title":"J Pediatr"},{"key":"2021052811195304800_CIT0005","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1002\/jmv.21455","article-title":"Predominant human herpesvirus 6 variant A infant infections in an HIV-1 endemic region of Sub-Saharan Africa","volume":"81","author":"Bates","year":"2009","journal-title":"J Med Virol"},{"key":"2021052811195304800_CIT0006","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1002\/jmv.20113","article-title":"Human herpesvirus 6 (HHV-6) is transmitted from parent to child in an integrated form and characterization of cases with chromosomally integrated HHV-6 DNA","volume":"73","author":"Tanaka-Taya","year":"2004","journal-title":"J Med Virol"},{"key":"2021052811195304800_CIT0007","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1002\/jmv.25244","article-title":"Chromosomally integrated human herpesvirus 6 in the Japanese population","volume":"90","author":"Miura","year":"2018","journal-title":"J Med Virol"},{"key":"2021052811195304800_CIT0008","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1111\/j.1399-3062.2011.00715.x","article-title":"Chromosomally integrated human herpesvirus-6 in transplant recipients","volume":"14","author":"Lee","year":"2012","journal-title":"Transpl Infect Dis"},{"key":"2021052811195304800_CIT0009","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/jmv.20760","article-title":"The prevalence of chromosomally integrated human herpesvirus 6 genomes in the blood of UK blood donors","volume":"79","author":"Leong","year":"2007","journal-title":"J Med Virol"},{"key":"2021052811195304800_CIT0010","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1002\/jmv.20399","article-title":"Unexpected occasional persistence of high levels of HHV-6 DNA in sera: detection of variants A and B","volume":"76","author":"Ward","year":"2005","journal-title":"J Med Virol"},{"key":"2021052811195304800_CIT0011","doi-asserted-by":"crossref","first-page":"e93","DOI":"10.1086\/593315","article-title":"Severe encephalomyelitis in an immunocompetent adult with chromosomally integrated human herpesvirus 6 and clinical response to treatment with foscarnet plus ganciclovir","volume":"47","author":"Troy","year":"2008","journal-title":"Clin Infect Dis"},{"key":"2021052811195304800_CIT0012","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1111\/j.1365-2141.2009.07641.x","article-title":"Human herpes virus-6 DNA in cerebrospinal fluid of children undergoing therapy for acute leukaemia","volume":"145","author":"Wittekindt","year":"2009","journal-title":"Br J Haematol"},{"key":"2021052811195304800_CIT0013","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.jcv.2012.05.016","article-title":"Antiviral therapy of two patients with chromosomally-integrated human herpesvirus-6A presenting with cognitive dysfunction","volume":"55","author":"Montoya","year":"2012","journal-title":"J Clin Virol"},{"key":"2021052811195304800_CIT0014","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1002\/jmv.23685","article-title":"Persistent human herpesvirus-6 infection in patients with an inherited form of the virus","volume":"85","author":"Pantry","year":"2013","journal-title":"J Med Virol"},{"key":"2021052811195304800_CIT0015","doi-asserted-by":"crossref","first-page":"8058","DOI":"10.1073\/pnas.1502741112","article-title":"Inherited chromosomally integrated human herpesvirus 6 as a predisposing risk factor for the development of angina pectoris","volume":"112","author":"Gravel","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2021052811195304800_CIT0016","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1093\/cid\/ciu323","article-title":"Molecular and virological evidence of viral activation from chromosomally integrated human herpesvirus 6A in a patient with X-linked severe combined immunodeficiency","volume":"59","author":"Endo","year":"2014","journal-title":"Clin Infect Dis"},{"key":"2021052811195304800_CIT0017","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1086\/650495","article-title":"Transplacental congenital human herpesvirus 6 infection caused by maternal chromosomally integrated virus","volume":"201","author":"Hall","year":"2010","journal-title":"J Infect Dis"},{"key":"2021052811195304800_CIT0018","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1093\/infdis\/jit060","article-title":"Sequence analysis of transplacentally acquired human herpesvirus 6 DNA is consistent with transmission of a chromosomally integrated reactivated virus","volume":"207","author":"Gravel","year":"2013","journal-title":"J Infect Dis"},{"key":"2021052811195304800_CIT0019","doi-asserted-by":"crossref","first-page":"5563","DOI":"10.1073\/pnas.0913586107","article-title":"The latent human herpesvirus-6A genome specifically integrates in telomeres of human chromosomes in vivo and in vitro","volume":"107","author":"Arbuckle","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2021052811195304800_CIT0020","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1182\/blood-2017-03-775759","article-title":"Outcomes of hematopoietic cell transplantation using donors or recipients with inherited chromosomally integrated HHV-6","volume":"130","author":"Hill","year":"2017","journal-title":"Blood"},{"key":"2021052811195304800_CIT0021","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1111\/tid.12419","article-title":"Virological analysis of inherited chromosomally integrated human herpesvirus-6 in three hematopoietic stem cell transplant patients","volume":"17","author":"Miura","year":"2015","journal-title":"Transpl Infect Dis"},{"key":"2021052811195304800_CIT0022","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1038\/sj.bmt.1702710","article-title":"Monitoring four herpesviruses in unrelated cord blood transplantation","volume":"26","author":"Tanaka","year":"2000","journal-title":"Bone Marrow Transplant"},{"key":"2021052811195304800_CIT0023","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.jviromet.2008.07.004","article-title":"Loop-mediated isothermal amplification for discriminating between human herpesvirus 6 A and B","volume":"154","author":"Ihira","year":"2008","journal-title":"J Virol Methods"},{"key":"2021052811195304800_CIT0024","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.jviromet.2015.11.001","article-title":"A simple cytogenetic method to detect chromosomally integrated human herpesvirus-6","volume":"228","author":"Ohye","year":"2016","journal-title":"J Virol Methods"},{"key":"2021052811195304800_CIT0025","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1542\/peds.2007-2838","article-title":"Chromosomal integration of human herpesvirus 6 is the major mode of congenital human herpesvirus 6 infection","volume":"122","author":"Hall","year":"2008","journal-title":"Pediatrics"},{"key":"2021052811195304800_CIT0026","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3390\/v8010019","article-title":"Complete genome sequence of germline chromosomally integrated human herpesvirus 6A and analyses integration sites define a new human endogenous virus with potential to reactivate as an emerging infection","volume":"8","author":"Tweedy","year":"2016","journal-title":"Viruses"},{"key":"2021052811195304800_CIT0027","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1099\/jgv.0.000834","article-title":"Analysis of the origin of inherited chromosomally integrated human herpesvirus 6 in the Japanese population","volume":"98","author":"Kawamura","year":"2017","journal-title":"J Gen Virol"},{"key":"2021052811195304800_CIT0028","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1186\/s12864-018-4604-2","article-title":"Comparative genomic, transcriptomic, and proteomic reannotation of human herpesvirus 6","volume":"19","author":"Greninger","year":"2018","journal-title":"BMC Genomics"},{"key":"2021052811195304800_CIT0029","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/bdra.23014","article-title":"A systematic review to calculate background miscarriage rates using life table analysis","volume":"94","author":"Ammon Avalos","year":"2012","journal-title":"Birth Defects Res A Clin Mol Teratol"},{"key":"2021052811195304800_CIT0030","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1056\/NEJM198807283190401","article-title":"Incidence of early loss of pregnancy","volume":"319","author":"Wilcox","year":"1988","journal-title":"N Engl J Med"},{"key":"2021052811195304800_CIT0031","doi-asserted-by":"crossref","first-page":"l869","DOI":"10.1136\/bmj.l869","article-title":"Role of maternal age and pregnancy history in risk of miscarriage: prospective register based study","volume":"364","author":"Magnus","year":"2019","journal-title":"BMJ"},{"key":"2021052811195304800_CIT0032","doi-asserted-by":"crossref","first-page":"331","DOI":"10.2147\/IJWH.S100817","article-title":"Recurrent pregnancy loss: current perspectives","volume":"9","author":"El Hachem","year":"2017","journal-title":"Int J Womens Health"},{"key":"2021052811195304800_CIT0033","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1016\/0140-6736(92)92990-W","article-title":"HHV-6 infection during pregnancy and spontaneous abortion","volume":"340","author":"Ando","year":"1992","journal-title":"Lancet"},{"key":"2021052811195304800_CIT0034","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.jcv.2011.02.001","article-title":"Detection of HHV-6 in over a thousand samples: new types of infection revealed by an analysis of positive results","volume":"51","author":"Revest","year":"2011","journal-title":"J Clin Virol"},{"key":"2021052811195304800_CIT0035","doi-asserted-by":"crossref","first-page":"S78","DOI":"10.1016\/j.jaad.2007.05.030","article-title":"Pregnancy outcome in patients with pityriasis rosea","volume":"58","author":"Drago","year":"2008","journal-title":"J Am Acad Dermatol"},{"key":"2021052811195304800_CIT0036","doi-asserted-by":"crossref","first-page":"e0158304","DOI":"10.1371\/journal.pone.0158304","article-title":"Presence of HHV-6A in endometrial epithelial cells from women with primary unexplained infertility","volume":"11","author":"Marci","year":"2016","journal-title":"PLoS One"},{"key":"2021052811195304800_CIT0037","doi-asserted-by":"crossref","first-page":"e13174","DOI":"10.1111\/aji.13174","article-title":"HHV-6A infection of endometrial epithelial cells affects immune profile and trophoblast invasion","volume":"82","author":"Bortolotti","year":"2019","journal-title":"Am J Reprod Immunol"},{"key":"2021052811195304800_CIT0038","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.3389\/fmicb.2017.02525","article-title":"HHV-6A infection of endometrial epithelial cells induces increased endometrial NK cell-mediated cytotoxicity","volume":"8","author":"Caselli","year":"2017","journal-title":"Front Microbiol"},{"key":"2021052811195304800_CIT0039","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1007\/s43032-019-00102-8","article-title":"HHV-6A infection of endometrial epithelial cells affects miRNA expression and trophoblast cell attachment","volume":"27","author":"Bortolotti","year":"2020","journal-title":"Reprod Sci"},{"key":"2021052811195304800_CIT0040","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1038\/s41564-020-0711-3","article-title":"Fetal inheritance of chromosomally integrated human herpesvirus 6 predisposes the mother to pre-eclampsia","volume":"5","author":"Gaccioli","year":"2020","journal-title":"Nat Microbiol"},{"key":"2021052811195304800_CIT0041","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.bbmt.2019.10.023","article-title":"Inflammatory cytokine profile in individuals with inherited chromosomally integrated human herpesvirus 6","volume":"26","author":"Weschke","year":"2020","journal-title":"Biol Blood Marrow Transplant"},{"key":"2021052811195304800_CIT0042","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1007\/s11262-020-01745-5","article-title":"Inherited chromosomally integrated HHV-6 possibly modulates human gene expression","volume":"56","author":"Kumata","year":"2020","journal-title":"Virus Genes"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiaa606\/34037522\/jiaa606.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jid\/article-pdf\/223\/10\/1717\/38360158\/jiaa606.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jid\/article-pdf\/223\/10\/1717\/38360158\/jiaa606.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T08:28:20Z","timestamp":1622190500000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/223\/10\/1717\/5912305"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,28]]},"references-count":42,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,9,28]]},"published-print":{"date-parts":[[2021,5,28]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiaa606","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,5,15]]},"published":{"date-parts":[[2020,9,28]]}}}