{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T12:58:01Z","timestamp":1755694681191,"version":"3.37.3"},"reference-count":65,"publisher":"Microbiology Society","issue":"12","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 AI112911-01"],"award-info":[{"award-number":["R01 AI112911-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["P01 AI112522-01"],"award-info":[{"award-number":["P01 AI112522-01"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,12,1]]},"abstract":"<jats:p>CD34+ myeloid lineage progenitor cells are an important reservoir of latent human cytomegalovirus (HCMV), and differentiation to macrophages or dendritic cells (DCs) is known to cause reactivation of latent virus. Due to its species-specificity, murine models have been used to study mouse CMV (MCMV) latency and reactivation <jats:italic>in vivo<\/jats:italic>. While previous studies have shown that MCMV genomic DNA can be detected in the bone marrow (BM) of latently infected mice, the identity of these cells has not been defined. Therefore, we sought to identify and enrich for cellular sites of MCMV latency in the BM haematopoietic system, and to explore the potential for establishing an <jats:italic>in vitro<\/jats:italic> model for reactivation of latent MCMV. We studied the kinetics and cellular characteristics of acute infection and establishment of latency in the BM of mice. We found that while MCMV can infect a broad range of haematopoietic BM cells (BMCs), latent virus is only detectable in haematopoietic stem cells (HSCs), myeloid progenitor cells, monocytes and DC-enriched cell subsets. Using three separate approaches, MCMV reactivation was detected in association with differentiation into DC-enriched BMCs cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) followed by lipopolysaccharide (LPS) treatment. In summary, we have defined the kinetics and cellular profile of MCMV infection followed by the natural establishment of latency <jats:italic>in vivo<\/jats:italic> in the mouse BM haematopoietic system, including the haematopoietic phenotypes of cells that are permissive to acute infection, establish and harbour detectable latent virus, and can be stimulated to reactivate following DC enrichment and differentiation, followed by treatment with LPS.<\/jats:p>","DOI":"10.1099\/jgv.0.001327","type":"journal-article","created":{"date-parts":[[2019,10,24]],"date-time":"2019-10-24T15:12:26Z","timestamp":1571929946000},"page":"1680-1694","source":"Crossref","is-referenced-by-count":11,"title":["A novel murine model of differentiation-mediated cytomegalovirus reactivation from latently infected bone marrow haematopoietic cells"],"prefix":"10.1099","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0878-4412","authenticated-orcid":false,"given":"Xue-feng","family":"Liu","sequence":"first","affiliation":[{"name":"Comprehensive Transplant Center, Departments of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suchitra","family":"Swaminathan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shixian","family":"Yan","sequence":"additional","affiliation":[{"name":"Comprehensive Transplant Center, Departments of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flora","family":"Engelmann","sequence":"additional","affiliation":[{"name":"Comprehensive Transplant Center, Departments of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darryl Adelaide","family":"Abbott","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luke Andrew","family":"VanOsdol","sequence":"additional","affiliation":[{"name":"Comprehensive Transplant Center, Departments of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0856-4006","authenticated-orcid":false,"given":"Taylor","family":"Heald-Sargent","sequence":"additional","affiliation":[{"name":"Division of Pediatric Infectious Diseases, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3122-9679","authenticated-orcid":false,"given":"Longhui","family":"Qiu","sequence":"additional","affiliation":[{"name":"Comprehensive Transplant Center, Departments of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9078-267X","authenticated-orcid":false,"given":"Andre","family":"Iovane","sequence":"additional","affiliation":[{"name":"Comprehensive Transplant Center, Departments of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Comprehensive Transplant Center, Departments of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9333-463X","authenticated-orcid":false,"given":"Michael M.","family":"Abecassis","sequence":"additional","affiliation":[{"name":"Comprehensive Transplant Center, Departments of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"},{"name":"Department of Microbiology and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2013.09.004"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1016\/S0950-3536(05)80236-7"},{"key":"R3","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1182\/blood.V88.4.1277.bloodjournal8841277","article-title":"Direct infection of CD34+ progenitor cells by human cytomegalovirus: evidence for inhibition of hematopoiesis and viral replication","volume":"88","author":"Movassagh","year":"1996","journal-title":"Blood"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.4.1386"},{"key":"R5","doi-asserted-by":"crossref","first-page":"4086","DOI":"10.1182\/blood.V86.11.4086.bloodjournal86114086","article-title":"Detection of cytomegalovirus DNA in CD34+ cells from blood and bone marrow","volume":"86","author":"von Laer","year":"1995","journal-title":"Blood"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-77-12-3099"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2004.05056.x"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-72-9-2059"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-74-2-265"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.05878-11"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0408994102"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.16.7543-7554.2001"},{"key":"R13","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1128\/JVI.68.3.1597-1604.1994","article-title":"Induction of endogenous human cytomegalovirus gene expression after differentiation of monocytes from healthy carriers","volume":"68","author":"Taylor-Wiedeman","year":"1994","journal-title":"J Virol"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00598-12"},{"key":"R15","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1128\/JVI.61.2.526-533.1987","article-title":"Immediate-early genes of murine cytomegalovirus: location, transcripts, and translation products","volume":"61","author":"Keil","year":"1987","journal-title":"J Virol"},{"key":"R16","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1128\/JVI.61.6.1901-1908.1987","article-title":"Sequence and structural organization of murine cytomegalovirus immediate-early gene 1","volume":"61","author":"Keil","year":"1987","journal-title":"J Virol"},{"key":"R17","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1128\/JVI.66.1.27-36.1992","article-title":"Structural organization, expression, and functional characterization of the murine cytomegalovirus immediate-early gene 3","volume":"66","author":"Messerle","year":"1992","journal-title":"J Virol"},{"key":"R18","first-page":"2629","volume-title":"Fields Virology","author":"Mocarski","year":"2001"},{"key":"R19","first-page":"513","article-title":"Mouse cytomegalovirus infection induces antibodies which cross-react with virus and cardiac myosin: a model for the study of molecular mimicry in the pathogenesis of viral myocarditis","volume":"75","author":"Lawson","year":"1992","journal-title":"Immunology"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1016\/S1386-6532(02)00088-4"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1186\/1471-213X-6-42"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-8-70"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-788-4_16"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.000339"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01941-14"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/155.2.207"},{"key":"R27","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1182\/blood.V86.2.473.bloodjournal862473","article-title":"Analysis of hematopoietic stem and progenitor cell populations in cytomegalovirus-infected mice","volume":"86","author":"Gibbons","year":"1995","journal-title":"Blood"},{"key":"R28","doi-asserted-by":"crossref","first-page":"3565","DOI":"10.1182\/blood.V89.10.3565","article-title":"Fas-mediated apoptosis of the hematopoietic progenitor cells in mice infected with murine cytomegalovirus","volume":"89","author":"Mori","year":"1997","journal-title":"Blood"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1996.8303"},{"key":"R30","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1128\/JVI.72.1.95-103.1998","article-title":"Cellular localization of latent murine cytomegalovirus","volume":"72","author":"Koffron","year":"1998","journal-title":"J Virol"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-24-10948.1999"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1002\/cpim.51"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2011.06.003"},{"key":"R34","first-page":"29","article-title":"Growing murine bone marrow-derived macrophages","volume":"2018","author":"Assouvie","year":"1784","journal-title":"Methods Mol Biol"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(98)00204-X"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02380-09"},{"key":"R37","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1128\/JVI.57.2.497-504.1986","article-title":"Pathogenesis of acute murine cytomegalovirus infection in resistant and susceptible strains of mice","volume":"57","author":"Mercer","year":"1986","journal-title":"J Virol"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.41.100187.002551"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3184"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1369\/0022155411416007"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2012.02.008"},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2006.00820.x"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-008-0094-1"},{"key":"R44","first-page":"305","article-title":"Apoptosis of hemopoietic cells in irradiated mouse bone marrow","volume":"18","author":"Peng","year":"1999","journal-title":"J Environ Pathol Toxicol Oncol"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2013.08.002"},{"key":"R46","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-472X(99)00029-6"},{"key":"R47","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.81161-0"},{"key":"R48","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1014509107"},{"key":"R49","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.8.5245"},{"key":"R50","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103426"},{"key":"R51","doi-asserted-by":"publisher","DOI":"10.1126\/science.2997930"},{"key":"R52","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.19.6134"},{"key":"R53","doi-asserted-by":"crossref","first-page":"6243","DOI":"10.1128\/JVI.68.10.6243-6253.1994","article-title":"Peripheral blood mononuclear phagocytes mediate dissemination of murine cytomegalovirus","volume":"68","author":"Stoddart","year":"1994","journal-title":"J Virol"},{"key":"R54","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.02.002"},{"key":"R55","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01264-17"},{"key":"R56","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1996.0468"},{"key":"R57","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1182\/blood.V93.1.394","article-title":"Peripheral blood CD14(+) cells from healthy subjects carry a circular conformation of latent cytomegalovirus genome","volume":"93","author":"Bolovan-Fritts","year":"1999","journal-title":"Blood"},{"key":"R58","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.252630899"},{"key":"R59","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01278-12"},{"key":"R60","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-12-4344"},{"key":"R61","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.06068"},{"key":"R62","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-018-0131-9"},{"key":"R63","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-01-070078"},{"key":"R64","doi-asserted-by":"crossref","first-page":"4017","DOI":"10.1128\/JVI.68.6.4017-4021.1994","article-title":"Human cytomegalovirus infection of the monocyte\/macrophage lineage in bone marrow","volume":"68","author":"Minton","year":"1994","journal-title":"J Virol"},{"key":"R65","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.7.3937"}],"container-title":["Journal of General Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/jgv.0.001327?crawler=true","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,4]],"date-time":"2020-11-04T14:20:46Z","timestamp":1604499646000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/jgv.0.001327"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,1]]},"references-count":65,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2019,12,1]]}},"URL":"https:\/\/doi.org\/10.1099\/jgv.0.001327","relation":{},"ISSN":["0022-1317","1465-2099"],"issn-type":[{"type":"print","value":"0022-1317"},{"type":"electronic","value":"1465-2099"}],"subject":[],"published":{"date-parts":[[2019,12,1]]}}}