{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:17:14Z","timestamp":1789129034091,"version":"build-2803163510"},"reference-count":65,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32172823"],"award-info":[{"award-number":["32172823"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,2,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>Pseudorabies virus (PRV) is a porcine neurotropic alphaherpesvirus that infects peripheral tissues of its host, spreads into the nervous system, and establishes a life-long latency in neuronal cells. During productive infection, PRV replicates rapidly and causes pseudorabies or Aujeszky\u2019s disease. Reactivation from latent infection in the nervous system may lead to anterograde axonal transport of progeny virions, leading to recurrent infection of the epithelial layer and virus spread. Dexamethasone (DEX), a member of the glucocorticoid family that is widely used in clinical treatment as a high-efficiency glucocorticoid receptor (GR) agonist, is known to trigger reactivation of alphaherpesviruses like PRV and the closely related bovine alphaherpesvirus 1. In the current study, two cell type-dependent distinct regulatory mechanisms of glucocorticoid during PRV infection are described. In neuron-like cells, DEX upregulates expression of PRV IE180 and promotes viral productive infection. In addition, we found that GR activates the IE180 promoter by binding multiple GR response elements. The amino acids A465, P631, and I634 in GR were found to be critical for IE180 promoter activation. The impact of DEX on PRV productive infection in epithelial cells was also investigated. Interestingly, DEX was found to downregulate IE180 expression and suppress PRV infection in epithelial cells. Mechanistically, in epithelial cells, activation of the IE180 promoter by the VP16\/Oct-1 (octamer-binding transcription factor 1) complex was suppressed by DEX-mediated degradation of Oct-1 in epithelial cells. In summary, our work reveals two distinct, cell type-dependent biological functions of glucocorticoid during PRV infection in neuron-like and epithelial cells, respectively.<\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>Pseudorabies virus (PRV) can infect mucosal epithelium and the peripheral nervous system of its host, resulting in acute infection in epithelial cells and neuronal cells. In this study, we describe that glucocorticoid promotes PRV replication in neuron-like cells while it suppresses productive infection in epithelial cells through distinct regulations of the viral transactivator IE180, thereby revealing a cell type-dependent regulatory mechanism of glucocorticoid on PRV infection. Therefore, our findings provide a new perspective on the role of glucocorticoids during PRV infection.<\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/jvi.01472-24","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T14:00:27Z","timestamp":1737727227000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["Distinct effects of glucocorticoid on pseudorabies virus infection in neuron-like and epithelial cells"],"prefix":"10.1128","volume":"99","author":[{"given":"Zhengmin","family":"Lian","sequence":"first","affiliation":[{"name":"Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University","place":["Yangzhou, 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