{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:52:28Z","timestamp":1783039948377,"version":"3.54.6"},"reference-count":53,"publisher":"National Academy of Sciences","issue":"24","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010446","name":"Institute for Basic Science","doi-asserted-by":"publisher","award":["IBS-R008-D1"],"award-info":[{"award-number":["IBS-R008-D1"]}],"id":[{"id":"10.13039\/501100010446","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2020R1A2C3011298"],"award-info":[{"award-number":["NRF-2020R1A2C3011298"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2020-NR049538"],"award-info":[{"award-number":["RS-2020-NR049538"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,6,17]]},"abstract":"<jats:p>\n                    Human cytomegalovirus (HCMV) is a prevalent pathogen that chronically infects the majority of human population. Among the many features that allow such widespread HCMV infection, one is its ability to maintain a transcriptionally dormant immune-evasive state called latency by suppressing its own major immediate early promoter (MIEP) via epigenetic alterations. In this study, we show a mechanism of MIEP regulation in which the major immediate early (MIE) gene product, immediate early 1 (IE1) transcript, downregulates its own promoter activity in an m\n                    <jats:sup>6<\/jats:sup>\n                    A modification-dependent manner. We found that the loss of the m\n                    <jats:sup>6<\/jats:sup>\n                    A writer, METTL3, in host cells impedes latency establishment in these cells. Through transcriptome-wide m\n                    <jats:sup>6<\/jats:sup>\n                    A profiling of latently infected monocytes, we identified that the major immediate early gene product IE1 transcript is m\n                    <jats:sup>6<\/jats:sup>\n                    A-modified during latent infection. Using IE1-specific m\n                    <jats:sup>6<\/jats:sup>\n                    A-abolished mutants, we found that m\n                    <jats:sup>6<\/jats:sup>\n                    A modification of the IE1 transcript was necessary for the efficient repression of MIEP, and these mutant viruses exhibited a significant defect in establishing latency and progressed toward lytic-like infection in the human monocytic cell line (THP-1) and primary CD14+ monocytes. Our findings demonstrate that HCMV exploits the host m\n                    <jats:sup>6<\/jats:sup>\n                    A machinery to suppress its own lytic program to establish latency and uncover an unexpected role of immediate early gene messenger RNA (mRNA) in regulating its own expression.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2508475122","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T11:07:53Z","timestamp":1749553673000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":2,"title":["N6-methyladenosine modification of HCMV IE1 transcript promotes the repressive state of viral genome to achieve latent infection"],"prefix":"10.1073","volume":"122","author":[{"given":"Heena","family":"Jeong","sequence":"first","affiliation":[{"name":"School of Biological Sciences, Seoul National University","place":["Seoul, Republic of Korea"]},{"name":"Center for RNA Research, Institute for Basic Science","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagyeong","family":"Yeo","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8213-5977","authenticated-orcid":false,"given":"Hyeonseo","family":"Hwang","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhyun","family":"Park","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Seoul National University","place":["Seoul, Republic of Korea"]},{"name":"Center for RNA Research, Institute for Basic Science","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daehyun","family":"Baek","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1015-245X","authenticated-orcid":false,"given":"Kwangseog","family":"Ahn","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Seoul National University","place":["Seoul, Republic of Korea"]},{"name":"Center for RNA Research, Institute for Basic Science","place":["Seoul, Republic of Korea"]},{"name":"Institute for Virus Research, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511545313"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.6.4017-4021.1994"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01278-12"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2007.11.014"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.3.1597-1604.1994"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.16.7543-7554.2001"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.259"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1501164"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","DOI":"10.1128\/mbio.00326-23","article-title":"Chromatin control of human cytomegalovirus infection","volume":"14","author":"Matthews S. 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Jeong N6-methyladenosine modification of HCMV IE1 transcript promotes the repressive state of viral genome to achieve latent infection. GEO. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE279262. 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