{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T08:27:37Z","timestamp":1778401657435,"version":"3.51.4"},"reference-count":44,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T00:00:00Z","timestamp":1719532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Council","award":["MR\/R021384\/1"],"award-info":[{"award-number":["MR\/R021384\/1"]}]},{"name":"Medical Research Council","award":["WT204870\/Z\/16\/Z\/WT"],"award-info":[{"award-number":["WT204870\/Z\/16\/Z\/WT"]}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["MR\/R021384\/1"],"award-info":[{"award-number":["MR\/R021384\/1"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT204870\/Z\/16\/Z\/WT"],"award-info":[{"award-number":["WT204870\/Z\/16\/Z\/WT"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Human cytomegalovirus (HCMV) primary infection, re-infection, and reactivation from latency cause morbidity in immune-compromised patients. Consequently, potential therapeutic strategies remain of interest for the treatment of infection. Naturally occurring triterpenoids derived from plants have been demonstrated to have anti-viral activity, although their precise mechanisms of action are not always fully understood. Here, we investigate the activity of Mormordin Ic (Mc) and demonstrate that it is potently anti-viral against HCMV. Through investigation of the mechanistic basis of this anti-viral activity, we identify that it is inhibitory to both viral and host gene expression, and to highly induced genes in particular. We go on to observe that Mc impacts on RNA Pol II activity and, specifically, reduces the occupancy of elongating RNA Pol II at a viral promoter. Next, we demonstrate that Mc is inhibitory to HCMV reactivation, and in doing so identify that it has greater activity against the canonical major immediate early promoter compared to the alternative ip2 promoter located downstream. Finally, we see evidence of RNA Pol II occupancy at the ip2 promoter in undifferentiated myeloid cells. Thus, Mc is potently anti-viral and a potential tool to probe the activity of multiple promoters considered important for controlling HCMV reactivation.<\/jats:p>","DOI":"10.3390\/pathogens13070546","type":"journal-article","created":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T03:42:30Z","timestamp":1719546150000},"page":"546","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Triterpenoid MOMORDIN-Ic Inhibits HCMV by Preventing the Initiation of Gene Expression in Eukaryotic Cells"],"prefix":"10.3390","volume":"13","author":[{"given":"Eleanor","family":"Bradley","sequence":"first","affiliation":[{"name":"Institute of Immunity & Transplantation, Division of Infection & Immunity, UCL, Royal Free Campus, London NW3 2PP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Poole","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke\u2019s Campus, Cambridge CB2 0QQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4909-1076","authenticated-orcid":false,"given":"Matthew B.","family":"Reeves","sequence":"additional","affiliation":[{"name":"Institute of Immunity & Transplantation, Division of Infection & Immunity, UCL, Royal Free Campus, London NW3 2PP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/s41579-021-00582-z","article-title":"Pathogenesis of human cytomegalovirus in the immunocompromised host","volume":"19","author":"Griffiths","year":"2021","journal-title":"Nat. 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