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While HCMV likely reactivates frequently and sporadically in healthy individuals and typically without disease, reactivation poses a serious disease threat in the immunocompromised. The latent program of HCMV is complex and has been challenging to define due to limitations in appropriate experimental model systems related to virus-host species specificity, limited identification of\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      latent reservoirs, and the dynamic cellular differentiation of the hematopoietic latency reservoir that is directly linked to latency maintenance and reactivation phenotypes. Here, we review the current understanding of HCMV latency, with a focus on cross-cutting principles derived collectively from\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      experimental culture models and\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      animal models using the corresponding orthologs (CMVs) to HCMV.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00664-25","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:01:08Z","timestamp":1753880468000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["Cytomegalovirus latency\u2014the sum of subtleties"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2945-0147","authenticated-orcid":true,"given":"Meaghan H.","family":"Hancock","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00d4pqn65","id-type":"ROR","asserted-by":"publisher"}],"name":"Vaccine and Gene Therapy Institute, Oregon Health and Science Institute","place":["Beaverton, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Caposio","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00d4pqn65","id-type":"ROR","asserted-by":"publisher"}],"name":"Vaccine and Gene Therapy Institute, Oregon Health and Science Institute","place":["Beaverton, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Collins-McMillen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth","place":["Lebanon, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8007-7865","authenticated-orcid":true,"given":"Nicole L.","family":"Diggins","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00d4pqn65","id-type":"ROR","asserted-by":"publisher"}],"name":"Vaccine and Gene Therapy Institute, Oregon Health and Science Institute","place":["Beaverton, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byeong-Jae","family":"Lee","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05ect4e57","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Louisiana State University Health Sciences Center","place":["Shreveport, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Medica","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00d4pqn65","id-type":"ROR","asserted-by":"publisher"}],"name":"Vaccine and Gene Therapy Institute, Oregon Health and Science Institute","place":["Beaverton, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6828-2492","authenticated-orcid":true,"given":"Daniel N.","family":"Streblow","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00d4pqn65","id-type":"ROR","asserted-by":"publisher"}],"name":"Vaccine and Gene Therapy Institute, Oregon Health and Science Institute","place":["Beaverton, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"White","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth","place":["Lebanon, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6452-5813","authenticated-orcid":true,"given":"Andrew D.","family":"Yurochko","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05ect4e57","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Louisiana State University Health Sciences Center","place":["Shreveport, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6646-7290","authenticated-orcid":true,"given":"Felicia","family":"Goodrum","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth","place":["Lebanon, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0065-230x(08)60089-5"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/9781555819521"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","unstructured":"Rozman B Nachshon A Samia RL Lavi M Schwartz M Stern-Ginossar N. 2021. 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