{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:31:37Z","timestamp":1790076697627,"version":"4.0.1"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2016,5,4]],"date-time":"2016-05-04T00:00:00Z","timestamp":1462320000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI079059"],"award-info":[{"award-number":["AI079059"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI21640"],"award-info":[{"award-number":["AI21640"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2016,5,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Human cytomegalovirus (HCMV), a betaherpesvirus, persists indefinitely in the human host through poorly understood mechanisms. The\n                    <jats:italic>UL136<\/jats:italic>\n                    gene is carried within a genetic locus important to HCMV latency termed the\n                    <jats:italic>UL133<\/jats:italic>\n                    \/\n                    <jats:italic>8<\/jats:italic>\n                    locus, which also carries\n                    <jats:italic>UL133<\/jats:italic>\n                    ,\n                    <jats:italic>UL135<\/jats:italic>\n                    , and\n                    <jats:italic>UL138<\/jats:italic>\n                    . Previously, we demonstrated that\n                    <jats:italic>UL136<\/jats:italic>\n                    is expressed as five protein isoforms ranging from 33-kDa to 19-kDa, arising from alternative transcription and, likely, translation initiation mechanisms. We previously showed that the\n                    <jats:italic>UL136<\/jats:italic>\n                    isoforms are largely dispensable for virus infection in fibroblasts, a model for productive virus replication. In our current work,\n                    <jats:italic>UL136<\/jats:italic>\n                    has emerged as a complex regulator of HCMV infection in multiple contexts of infection relevant to HCMV persistence: in an endothelial cell (EC) model of chronic infection, in a CD34\n                    <jats:sup>+<\/jats:sup>\n                    hematopoietic progenitor cell (HPC) model of latency, and in an\n                    <jats:italic>in vivo<\/jats:italic>\n                    NOD-\n                    <jats:italic>scid<\/jats:italic>\n                    IL2R\u03b3\n                    <jats:sub>c<\/jats:sub>\n                    <jats:sup>null<\/jats:sup>\n                    humanized (huNSG) mouse model for latency. The 33- and 26-kDa isoforms promote replication, while the 23- and 19-kDa isoforms suppress replication in ECs, in CD34\n                    <jats:sup>+<\/jats:sup>\n                    HPCs, and in huNSG mice. The role of the 25-kDa isoform is context dependent and influences the activity of the other isoforms. These isoforms localize throughout the secretory pathway, and loss of the 33- and 26-kDa\n                    <jats:italic>UL136<\/jats:italic>\n                    isoforms results in virus maturation defects in ECs. This work reveals an intriguing functional interplay between protein isoforms that impacts virus replication, latency, and dissemination, contributing to the overall role of the\n                    <jats:italic>UL133<\/jats:italic>\n                    \/\n                    <jats:italic>8<\/jats:italic>\n                    locus in HCMV infection.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    The persistence of DNA viruses, and particularly of herpesviruses, remains an enigma because we have not completely defined the viral and host factors important to persistence. Human cytomegalovirus, a herpesvirus, persists in the absence of disease in immunocompetent individuals but poses a serious disease threat to transplant patients and the developing fetus. There is no vaccine, and current therapies do not target latent reservoirs. In an effort to define the viral factors important to persistence, we have studied viral genes with no known viral replication function in contexts important to HCMV persistence. Using models relevant to viral persistence, we demonstrate opposing roles of protein isoforms encoded by the\n                    <jats:italic>UL136<\/jats:italic>\n                    gene in regulating latent and replicative states of infection. Our findings reveal an intriguing interplay between\n                    <jats:italic>UL136<\/jats:italic>\n                    protein isoforms and define\n                    <jats:italic>UL136<\/jats:italic>\n                    as an important regulator of HCMV persistence.\n                  <\/jats:p>","DOI":"10.1128\/mbio.01986-15","type":"journal-article","created":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T22:03:54Z","timestamp":1456869834000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":51,"title":["Complex Interplay of the\n                    <i>UL136<\/i>\n                    Isoforms Balances Cytomegalovirus Replication and Latency"],"prefix":"10.1128","volume":"7","author":[{"given":"Katie","family":"Caviness","sequence":"first","affiliation":[{"name":"Graduate Interdisciplinary Program in Genetics, University of Arizona, Tucson, Arizona, USA"},{"name":"BIO5 Institute, University of Arizona, Tucson, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farah","family":"Bughio","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Arizona, Tucson, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey B.","family":"Crawford","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel N.","family":"Streblow","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay A.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Caposio","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicia","family":"Goodrum","sequence":"additional","affiliation":[{"name":"Graduate Interdisciplinary Program in Genetics, University of Arizona, Tucson, Arizona, USA"},{"name":"BIO5 Institute, University of Arizona, Tucson, Arizona, USA"},{"name":"Department of Cellular and Molecular Medicine, University of Arizona, Tucson, Arizona, USA"},{"name":"Department of Immunobiology, University of Arizona, Tucson, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2012.01774.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-77349-8_23"},{"key":"e_1_3_2_4_2","volume-title":"Fields\u2019 virology","author":"Mocarski ES","year":"2013","unstructured":"Mocarski ES, Shenk TE, Griffiths PD, Pass RF. 2013. 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