{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:22:37Z","timestamp":1791354157410,"version":"4.3.1"},"reference-count":383,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T00:00:00Z","timestamp":1579132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/P022146\/1"],"award-info":[{"award-number":["MR\/P022146\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The human cytomegalovirus (HCMV), one of eight human herpesviruses, establishes lifelong latent infections in most people worldwide. Primary or reactivated HCMV infections cause severe disease in immunosuppressed patients and congenital defects in children. There is no vaccine for HCMV, and the currently approved antivirals come with major limitations. Most approved HCMV antivirals target late molecular processes in the viral replication cycle including DNA replication and packaging. \u201cBright and early\u201d events in HCMV infection have not been exploited for systemic prevention or treatment of disease. Initiation of HCMV replication depends on transcription from the viral major immediate-early (IE) gene. Alternative transcripts produced from this gene give rise to the IE1 and IE2 families of viral proteins, which localize to the host cell nucleus. The IE1 and IE2 proteins are believed to control all subsequent early and late events in HCMV replication, including reactivation from latency, in part by antagonizing intrinsic and innate immune responses. Here we provide an update on the regulation of major IE gene expression and the functions of IE1 and IE2 proteins. We will relate this insight to experimental approaches that target IE gene expression or protein function via molecular gene silencing and editing or small chemical inhibitors.<\/jats:p>","DOI":"10.3390\/v12010110","type":"journal-article","created":{"date-parts":[[2020,1,17]],"date-time":"2020-01-17T04:14:41Z","timestamp":1579234481000},"page":"110","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Bright and Early: Inhibiting Human Cytomegalovirus by Targeting Major Immediate-Early Gene Expression or Protein Function"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7673-5212","authenticated-orcid":false,"given":"Catherine S.","family":"Adamson","sequence":"first","affiliation":[{"name":"School of Biology, Biomedical Sciences Research Complex, University of St Andrews, St Andrews KY16 9ST, Scotland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7115-407X","authenticated-orcid":false,"given":"Michael M.","family":"Nevels","sequence":"additional","affiliation":[{"name":"School of Biology, Biomedical Sciences Research Complex, University of St Andrews, St Andrews KY16 9ST, Scotland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6892","DOI":"10.1126\/science.aam6892","article-title":"Atomic structure of the human cytomegalovirus capsid with its securing tegument layer of pp150","volume":"356","author":"Yu","year":"2017","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Arvin, A., Campadelli-Fiume, G., Mocarski, E., Moore, P.S., Roizman, B., Whitley, R., and Yamanishi, K. 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