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It can be challenging to decipher how such effects contribute to the biological roles of the proteins. The HCMV glycoprotein UL148 retains CD58 within the ER, thereby preventing it from reaching the cell surface, where it functions to stimulate cell-mediated antiviral responses. Intriguingly, UL148 also triggers the formation of large, ER-derived membranous structures and activates the UPR, a set of signaling pathways involved in adaptation to ER stress. We demonstrate that the potential of UL148 to reorganize the ER and to retain CD58 are separable by mutagenesis and, possibly, by evolution, since chimpanzee cytomegalovirus UL148 retains CD58 but does not remodel the ER. Our findings imply that ER reorganization contributes to other roles of UL148, such as modulation of alternative viral glycoprotein complexes that govern the virus\u2019 ability to infect different cell types.<\/jats:p>","DOI":"10.1128\/jvi.01435-19","type":"journal-article","created":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T07:19:32Z","timestamp":1575357572000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Endoplasmic Reticulum (ER) Reorganization and Intracellular Retention of CD58 Are Functionally Independent Properties of the Human Cytomegalovirus ER-Resident Glycoprotein UL148"],"prefix":"10.1128","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3013-802X","authenticated-orcid":false,"given":"Christopher C.","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, LSU Health Sciences Center, Shreveport, Shreveport, Louisiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5279-9449","authenticated-orcid":false,"given":"Anthony J.","family":"Domma","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, LSU Health Sciences Center, Shreveport, Shreveport, Louisiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9689-9350","authenticated-orcid":false,"given":"Hongbo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, LSU Health Sciences Center, Shreveport, Shreveport, Louisiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8422-7656","authenticated-orcid":false,"given":"Jeremy P.","family":"Kamil","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, LSU Health Sciences Center, Shreveport, Shreveport, Louisiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2010.10.031"},{"key":"e_1_3_2_3_2","first-page":"1960","volume-title":"Fields\u2019 virology","author":"Mocarski ES","year":"2013","unstructured":"Mocarski ES, Shenk T, Griffiths PD, Pass RF. 2013. 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