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China","award":["18170032","T12-712\/21-R","1120222","2022","RC-IRCs-1718-03","FRG2\/17\u201318\/066","SCI-17-18-01","RC-SGT2\/18-19\/SCI\/007","82301945"],"award-info":[{"award-number":["18170032","T12-712\/21-R","1120222","2022","RC-IRCs-1718-03","FRG2\/17\u201318\/066","SCI-17-18-01","RC-SGT2\/18-19\/SCI\/007","82301945"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Human cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus that establishes lifelong latent infection in CD34+ haematopoietic stem and progenitor cells. A unique subset of viral genes is expressed during latency, which functions to modulate cellular mechanisms without supporting viral replication. One potential function of these genes is to regulate the differentiation state of latently infected CD34+ cells, thereby preventing their progression into antigen-presenting cells, e.g., dendritic cells. In this study, we first compared CD34+ cells that supported productive and latent infections using the RV-TB40-BACKL7-SE-EGFP virus. Over a seven-day time course, the proportion of latently infected CD34+ cell subsets within the myeloid progenitor population remained similar to that in the mock-infected control. However, starting from day 3 post-infection, there was an increase in the proportion of the early progenitor subsets, including haematopoietic stem cells (HSCs) and multipotent progenitors (MPPs). In contrast, productively infected cells, which constituted less than 1% of the population, only accounted for a small portion of the myeloid progenitors. Importantly, our data revealed that the innate immune STING\/p-TBK1\/p-IRF3 pathway was activated in latently infected CD34+ cells, yet type I interferon (IFN) expression was decreased. This decrease was attributed to impaired p-IRF3 nuclear translocation, limiting the induction of an autocrine type I IFN response. However, treatment with IFN-\u03b2 could induce myelopoiesis in latently infected cells. In summary, HCMV modulates a key component of the STING pathway to inhibit antiviral immune responses by decreasing the type I IFN-mediated cell differentiation of CD34+ progenitor cells. This study uncovered a new mechanism of latent HCMV-mediated regulation of the host cell differentiation response.<\/jats:p>","DOI":"10.3390\/v17081109","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T15:51:02Z","timestamp":1755013862000},"page":"1109","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Latent Human Cytomegalovirus Infection Activates the STING Pathway but p-IRF3 Translocation Is Limited"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3700-3681","authenticated-orcid":false,"given":"Wang Ka","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Biology, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9575-6198","authenticated-orcid":false,"given":"Zuodong","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8989-0537","authenticated-orcid":false,"given":"Allen Ka Loon","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1159\/000322141","article-title":"Human Cytomegalovirus (HCMV)\u2014Revised","volume":"37","author":"Schottstedt","year":"2010","journal-title":"Transfus. 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