{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T03:28:12Z","timestamp":1789097292485,"version":"build-2803163510"},"reference-count":130,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T00:00:00Z","timestamp":1703721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UIC College of Medicine Startup Funds"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Human cytomegalovirus (HCMV) has a broad cellular tropism and epithelial cells are important physiological targets during infection. The retinal pigment epithelial cell line ARPE-19 has been used to model HCMV infection in epithelial cells for decades and remains a commonly used cell type for studying viral entry, replication, and the cellular response to infection. We previously found that ARPE-19 cells, despite being derived from an epithelial cell explant, express extremely low levels of canonical epithelial proteins, such as E-cadherin and EpCAM. Here, we perform comparative studies of ARPE-19 and additional epithelial cell lines with strong epithelial characteristics. We find that ARPE-19 cells cultured under subconfluent conditions resemble mesenchymal fibroblasts, rather than epithelial cells; this is consistent with previous studies showing that ARPE-19 cultures require extended periods of high confluency culture to maintain epithelial characteristics. By reanalyzing public gene expression data and using machine learning, we find evidence that ARPE-19 cultures maintained across many labs exhibit mesenchymal characteristics and that the majority of studies employing ARPE-19 use them in a mesenchymal state. Lastly, by performing experimental HCMV infections across mesenchymal and epithelial cell lines, we find that ARPE-19 cells behave like mesenchymal fibroblasts, producing logarithmic yields of cell-free infectious progeny, while cell lines with strong epithelial character exhibit an atypical infectious cycle and naturally restrict the production of cell-free progeny. Our work highlights important characteristics of the ARPE-19 cell line and suggests that subconfluent ARPE-19 cells may not be optimal for modeling epithelial infection with HCMV or other human viruses. It also suggests that HCMV biosynthesis and\/or spread may occur quite differently in epithelial cells compared to mesenchymal cells. These differences could contribute to viral persistence or pathogenesis in epithelial tissues.<\/jats:p>","DOI":"10.3390\/v16010049","type":"journal-article","created":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T09:56:27Z","timestamp":1703757387000},"page":"49","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Subconfluent ARPE-19 Cells Display Mesenchymal Cell-State Characteristics and Behave like Fibroblasts, Rather Than Epithelial Cells, in Experimental HCMV Infection Studies"],"prefix":"10.3390","volume":"16","author":[{"given":"Preethi","family":"Golconda","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, 835 South Wolcott Ave., Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Andrade-Medina","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, 835 South Wolcott Ave., Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Oberstein","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, 835 South Wolcott Ave., Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Shenk, T., and Stinski, M. 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