{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T12:42:41Z","timestamp":1782564161275,"version":"3.54.5"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI182082"],"award-info":[{"award-number":["R01AI182082"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01AI132132"],"award-info":[{"award-number":["P01AI132132"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2R24OD017850"],"award-info":[{"award-number":["2R24OD017850"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Infection with clade I Mpox virus (MPXV) results in adverse pregnancy outcomes, yet the potential for vertical transmission resulting in fetal harm with clade IIb MPXV, the clade that is currently circulating in the Western Hemisphere, remains unknown. We sought to establish a pregnant rhesus macaque model of clade IIb MPXV infection with early gestation inoculation to understand if infection results in vertical transmission and adverse pregnancy outcomes. Three pregnant rhesus macaques were inoculated intradermally with 1.5 x 10<jats:sup>5<\/jats:sup> plaque forming units (PFU) of clade IIb MPXV near gestational day (GD) 30 and animals were monitored for viremia and maternal and fetal well-being. Animals were euthanized to collect tissues at 5, 14, or 25 days post-inoculation (dpi). Tissues were evaluated for viral DNA (vDNA) loads, infectious virus titers, histopathology, MPXV mRNA and protein localization, as well as MPXV protein co-localization with placental cells including, Hofbauer cells, mesenchymal stromal cells, endothelial cells, and trophoblasts. vDNA was detected in maternal blood and skin lesions by 5 dpi. Lack of fetal heartbeat was observed at 14 or 25 dpi for two dams indicating fetal demise; the third dam developed significant vaginal bleeding at 5 dpi and was deemed an impending miscarriage. vDNA was detected in placental and fetal tissue in both fetal demise cases. MPXV localized to placental villi by ISH and IHC. Clade IIb MPXV infection in pregnant rhesus macaques results in vertical transmission to the fetus and adverse pregnancy outcomes, like clade I MPXV. This suggests that clade IIb MPXV infection in human pregnancy poses a danger to maternal and fetal health as well. Further studies are needed to determine whether antiviral therapy with tecovirimat will prevent vertical transmission and improve pregnancy outcomes.<\/jats:p>","DOI":"10.1371\/journal.pone.0320671","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T21:22:59Z","timestamp":1743542579000},"page":"e0320671","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Clade IIb Mpox virus (MPXV) vertical transmission and fetal demise in a pregnant rhesus macaque model"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5511-0915","authenticated-orcid":true,"given":"Nicholas P.","family":"Krabbe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann M.","family":"Mitzey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saswati","family":"Bhattacharya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaina R.","family":"Razo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiankun","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nell","family":"Bekiares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Moy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Kamholz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Karl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Daggett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"VanSleet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saverio V.","family":"Capuano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4862-7289","authenticated-orcid":true,"given":"Heather A.","family":"Simmons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puja","family":"Basu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea M.","family":"Weiler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"O\u2019Connor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas C.","family":"Friedrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thaddeus G.","family":"Golos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0742-305X","authenticated-orcid":true,"given":"Emma L.","family":"Mohr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,4,1]]},"reference":[{"key":"pone.0320671.ref001","year":"2024"},{"key":"pone.0320671.ref002","article-title":"Mpox Virus in Pregnancy, the Placenta, and Newborn. An Emerging Poxvirus with Similarities to Smallpox and Other Orthopoxvirus Agents Causing Maternal and Fetal Disease","author":"DA Schwartz","year":"2023","journal-title":"Arch Pathol Lab Med [Internet]"},{"issue":"2","key":"pone.0320671.ref003","first-page":"165","article-title":"Human monkeypox, 1970-79","volume":"58","author":"J Breman","year":"1980","journal-title":"Bulletin of the World Health Organization"},{"issue":"2","key":"pone.0320671.ref004","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1093\/cid\/cit703","article-title":"Human monkeypox","volume":"58","author":"AM McCollum","year":"2014","journal-title":"Clin Infect Dis"},{"issue":"3","key":"pone.0320671.ref005","doi-asserted-by":"crossref","first-page":"432","DOI":"10.3201\/eid3003.230861","article-title":"Concurrent clade I and clade II monkeypox virus circulation, Cameroon, 1979-2022","volume":"30","author":"D Djuicy","year":"2024","journal-title":"Emerging Infectious Diseases"},{"key":"pone.0320671.ref006","author":"CDC","year":"2024"},{"key":"pone.0320671.ref007","author":"CDC","year":"2024"},{"issue":"4","key":"pone.0320671.ref008","doi-asserted-by":"crossref","first-page":"e572","DOI":"10.1016\/S2214-109X(23)00607-1","article-title":"Paediatric, maternal, and congenital mpox: a systematic review and meta-analysis","volume":"12","author":"N Sanchez Clemente","year":"2024","journal-title":"Lancet Glob Health"},{"key":"pone.0320671.ref009","author":"J Nachega","year":"2024"},{"issue":"7","key":"pone.0320671.ref010","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1093\/infdis\/jix260","article-title":"Maternal and Fetal Outcomes Among Pregnant Women With Human Monkeypox Infection in the Democratic Republic of Congo","volume":"216","author":"PK Mbala","year":"2017","journal-title":"J Infect Dis"},{"issue":"4","key":"pone.0320671.ref011","doi-asserted-by":"crossref","first-page":"e0010384","DOI":"10.1371\/journal.pntd.0010384","article-title":"Clinical characterization and placental pathology of mpox infection in hospitalized patients in the Democratic Republic of the Congo","volume":"17","author":"PR Pittman","year":"2023","journal-title":"PLoS Negl Trop Dis"},{"issue":"8","key":"pone.0320671.ref012","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.3390\/v15081649","article-title":"Mpox (Monkeypox) in Pregnancy: Viral Clade Differences and Their Associations with Varying Obstetrical and Fetal Outcomes","volume":"15","author":"DA Schwartz","year":"2023","journal-title":"Viruses"},{"key":"pone.0320671.ref013","doi-asserted-by":"crossref","first-page":"100523","DOI":"10.1016\/j.onehlt.2023.100523","article-title":"Investigation of a mpox outbreak in Central African Republic, 2021-2022","volume":"16","author":"C Besombes","year":"2023","journal-title":"One Health"},{"key":"pone.0320671.ref014","year":"2024"},{"issue":"1","key":"pone.0320671.ref015","doi-asserted-by":"crossref","first-page":"9","DOI":"10.15585\/mmwr.mm7201a2","article-title":"Mpox cases among cisgender women and pregnant persons - United States, May 11-November 7, 2022","volume":"72","author":"L Oakley","year":"2023","journal-title":"MMWR Morb Mortal Wkly Rep"},{"issue":"5","key":"pone.0320671.ref016","first-page":"1007","article-title":"Mpox (Monkeypox) Infection During Pregnancy","volume":"141","author":"MM Sampson","year":"2023","journal-title":"Obstet Gynecol"},{"issue":"6","key":"pone.0320671.ref017","doi-asserted-by":"crossref","first-page":"849-861.e7","DOI":"10.1016\/j.ajog.2022.08.017","article-title":"Monkeypox in pregnancy: virology, clinical presentation, and obstetric management","volume":"227","author":"P Dashraath","year":"2022","journal-title":"Am J Obstet Gynecol"},{"issue":"11","key":"pone.0320671.ref018","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1016\/S1473-3099(22)00612-0","article-title":"Monkeypox in pregnancy: update on current outbreak","volume":"22","author":"A Khalil","year":"2022","journal-title":"Lancet Infect Dis"},{"issue":"11","key":"pone.0320671.ref019","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/S2352-4642(22)00223-1","article-title":"The monkeypox outbreak: risks to children and pregnant women","volume":"6","author":"M Vouga","year":"2022","journal-title":"Lancet Child Adolesc Health"},{"issue":"2","key":"pone.0320671.ref020","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.ajog.2022.09.029","article-title":"Approach to monkeypox in pregnancy: conjecture is best guided by evidence","volume":"228","author":"D Baud","year":"2023","journal-title":"Am J Obstet Gynecol"},{"key":"pone.0320671.ref021","doi-asserted-by":"crossref","first-page":"63","DOI":"10.31300\/TDB.14.2021.63-72","article-title":"Maternal determinants of gestation length in the rhesus monkey","volume":"14","author":"CL Coe","year":"2021","journal-title":"Trends Dev Biol"},{"issue":"7","key":"pone.0320671.ref022","doi-asserted-by":"crossref","first-page":"4296","DOI":"10.1128\/AAC.00208-15","article-title":"Treatment with the smallpox antiviral tecovirimat (ST-246) alone or in combination with ACAM2000 vaccination is effective as a postsymptomatic therapy for monkeypox virus infection","volume":"59","author":"A Berhanu","year":"2015","journal-title":"Antimicrob Agents Chemother"},{"issue":"46","key":"pone.0320671.ref023","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.46234\/ccdcw2022.206","article-title":"Isolation and characterization of monkeypox virus from the first case of monkeypox - Chongqing Municipality, China, 2022","volume":"4","author":"B Huang","year":"2022","journal-title":"China CDC Weekly"},{"key":"pone.0320671.ref024","first-page":"246","volume-title":"National Research Council, Division on Earth and Life Studies, Institute for Laboratory Animal Research, Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals: Eighth Edition","year":"2011"},{"key":"pone.0320671.ref025"},{"issue":"1","key":"pone.0320671.ref026","doi-asserted-by":"crossref","first-page":"e0190617","DOI":"10.1371\/journal.pone.0190617","article-title":"Ocular and uteroplacental pathology in a macaque pregnancy with congenital Zika virus infection","volume":"13","author":"EL Mohr","year":"2018","journal-title":"PLoS One"},{"issue":"3","key":"pone.0320671.ref027","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.jcv.2006.03.012","article-title":"Detection of monkeypox virus with real-time PCR assays","volume":"36","author":"Y Li","year":"2006","journal-title":"J Clin Virol"},{"issue":"12","key":"pone.0320671.ref028","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1038\/s41564-022-01259-w","article-title":"Retrospective detection of monkeypox virus in the testes of nonhuman primate survivors","volume":"7","author":"J Liu","year":"2022","journal-title":"Nat Microbiol"},{"issue":"12","key":"pone.0320671.ref029","doi-asserted-by":"crossref","first-page":"8042","DOI":"10.4049\/jimmunol.179.12.8042","article-title":"Passive immunization against the MHC class I molecule Mamu-AG disrupts rhesus placental development and endometrial responses","volume":"179","author":"GI Bondarenko","year":"2007","journal-title":"J Immunol"},{"issue":"8","key":"pone.0320671.ref030","doi-asserted-by":"crossref","first-page":"e1011274","DOI":"10.1371\/journal.ppat.1011274","article-title":"Vertical transmission of African-lineage Zika virus through the fetal membranes in a rhesus macaque (Macaca mulatta) model","volume":"19","author":"MR Koenig","year":"2023","journal-title":"PLoS Pathog"},{"issue":"6","key":"pone.0320671.ref031","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/j.cell.2024.01.017","article-title":"A multivalent mRNA monkeypox virus vaccine (BNT166) protects mice and macaques from orthopoxvirus disease","volume":"187","author":"A Zuiani","year":"2024","journal-title":"Cell"},{"issue":"3","key":"pone.0320671.ref032","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.vaccine.2019.10.049","article-title":"Co-administration of tecovirimat and ACAM2000TM in non-human primates: Effect of tecovirimat treatment on ACAM2000 immunogenicity and efficacy versus lethal monkeypox virus challenge","volume":"38","author":"AT Russo","year":"2020","journal-title":"Vaccine"},{"issue":"9","key":"pone.0320671.ref033","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.3390\/v14091993","article-title":"Evaluation of Virulence in Cynomolgus Macaques Using a Virus Preparation Enriched for the Extracellular Form of Monkeypox Virus","volume":"14","author":"EM Mucker","year":"2022","journal-title":"Viruses [Internet]"},{"issue":"Pt 9","key":"pone.0320671.ref034","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1099\/vir.0.010207-0","article-title":"Virulence and pathophysiology of the Congo Basin and West African strains of monkeypox virus in non-human primates","volume":"90","author":"M Saijo","year":"2009","journal-title":"J Gen Virol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0320671","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T21:24:39Z","timestamp":1743542679000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0320671"}},"subtitle":[],"editor":[{"given":"Dhammika Leshan","family":"Wannigama","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,4,1]]},"references-count":34,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0320671","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,1]]}}}