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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,6,3]]},"abstract":"<jats:p>\n                    The human cytomegalovirus (HCMV)\n                    <jats:italic toggle=\"yes\">UL135<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">UL138<\/jats:italic>\n                    genes play opposing roles regulating latency and reactivation in CD34\n                    <jats:sup>+<\/jats:sup>\n                    human progenitor cells. We designed an RNA sequencing study to compare the transcriptional profile of HCMV infection in the presence and absence of these genes using the Tohoku Hospital Pediatrics-1 (THP-1) monocytic cell line model for latency. Relative to primary cell models, THP-1 cells offer the strength of a homogenous population that uniformly silences gene expression and will synchronously reexpress viral genes following stimulation to differentiate, which models early phases of viral reactivation. The loss of\n                    <jats:italic toggle=\"yes\">UL138<\/jats:italic>\n                    resulted in elevated levels of viral gene expression and in spontaneous adhesion of distinct cell populations that support HCMV gene expression and genome synthesis. The loss of\n                    <jats:italic toggle=\"yes\">UL135<\/jats:italic>\n                    resulted in diminished viral gene expression during an initial burst that occurs as latency is established and in no expression of eleven viral genes from the UL\n                    <jats:italic toggle=\"yes\">b<\/jats:italic>\n                    \u2032 region even following differentiation and reexpression of viral genes. Transcriptional network analysis revealed host transcription factors (TFs) with potential to regulate the UL\n                    <jats:italic toggle=\"yes\">b<\/jats:italic>\n                    \u2032 genes in coordination with pUL135. We show that the cellular TF peroxisome proliferator-activated receptor gamma binds to the viral genome and influences the expression of\n                    <jats:italic toggle=\"yes\">UL133-UL138<\/jats:italic>\n                    locus genes. Our results define roles for\n                    <jats:italic toggle=\"yes\">UL135<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">UL138<\/jats:italic>\n                    in regulation of patterns of viral gene expression for the establishment of latency and reexpression of viral genes for reactivation and reveal insights into differentiation-linked mechanisms of transcriptional control of the HCMV genome.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2416114122","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T11:06:42Z","timestamp":1748430402000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":11,"title":["Viral and host network analysis of the human cytomegalovirus transcriptome in latency"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6593-1912","authenticated-orcid":false,"given":"Donna","family":"Collins-McMillen","sequence":"first","affiliation":[{"name":"Bioscience Innovation Organization Five Disciplines (BIO5) Institute, University of Arizona","place":["Tucson"]},{"name":"Department of Immunobiology, University of Arizona","place":["Tucson"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diogo","family":"De Oliveira Pessoa","sequence":"additional","affiliation":[{"name":"Bioinformatics Shared Resource, Arizona Cancer Center, University of Arizona","place":["Tucson"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3142-6664","authenticated-orcid":false,"given":"Kristen","family":"Zarrella","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, University of Arizona","place":["Tucson"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Parkins","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health Science University","place":["Beaverton"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Daily","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health Science University","place":["Beaverton"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0845-5352","authenticated-orcid":false,"given":"David R.","family":"McKinzey","sequence":"additional","affiliation":[{"name":"Bioscience Innovation Organization Five Disciplines (BIO5) Institute, University of Arizona","place":["Tucson"]},{"name":"Department of Immunobiology, University of Arizona","place":["Tucson"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4952-6858","authenticated-orcid":false,"given":"Nathaniel J.","family":"Moorman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill","place":["Chapel Hill"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8422-7656","authenticated-orcid":false,"given":"Jeremy P.","family":"Kamil","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Louisiana State University Health Sciences Center","place":["Shreveport"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7579-849X","authenticated-orcid":false,"given":"Patrizia","family":"Caposio","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health Science University","place":["Beaverton"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3446-4562","authenticated-orcid":false,"given":"Megha","family":"Padi","sequence":"additional","affiliation":[{"name":"Bioinformatics Shared Resource, Arizona Cancer Center, University of Arizona","place":["Tucson"]},{"name":"University of Arizona Cancer Center, University of Arizona","place":["Tucson"]},{"name":"Department of Molecular and Cellular Biology, University of Arizona","place":["Tucson"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6646-7290","authenticated-orcid":false,"given":"Felicia D.","family":"Goodrum","sequence":"additional","affiliation":[{"name":"Bioscience Innovation Organization Five Disciplines (BIO5) Institute, University of Arizona","place":["Tucson"]},{"name":"Department of Immunobiology, University of Arizona","place":["Tucson"]},{"name":"University of Arizona Cancer Center, University of Arizona","place":["Tucson"]},{"name":"Department of Molecular and Cellular Biology, University of Arizona","place":["Tucson"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,5,28]]},"reference":[{"key":"e_1_3_4_1_2","unstructured":"F. 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