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Human cytomegalovirus (HCMV) uses myeloid cells as vehicles to facilitate viral dissemination. HCMV infection in monocytes and macrophages leads to the downregulation of several cell surface markers via an undefined mechanism. Previously, we showed that HCMV pUL42 associates with the Nedd4 family ubiquitin E3 ligases through the PPXY motif on pUL42 and downregulates Nedd4 and Itch proteins in HCMV\u2010infected fibroblasts. Homologous proteins of HCMV pUL42, such as HHV\u20106 U24, downregulate cell surface markers. To reveal the downregulation property of pUL42, we focused on CD86, the key costimulatory factor for acquired immunity. Here, we constructed CD86\u2010expressing THP\u20101 cells using a retroviral vector and analyzed the effects of HCMV infection and pUL42 on CD86 downregulation. Disruption of the PPXY motifs of pUL42 (UL42PA) decelerated the degradation of CD86 in recombinant virus\u2010infected cells, indicating the involvement of Nedd4 family functions. However, no direct interactions were observed between CD86 and Itch. Interestingly, unlike fibroblast infection, the expression of Nedd4 and Itch proteins increased in HCMV\u2010infected THP\u20101 cells, accompanied by an increase in their transcript levels. Although the function of pUL42 did not relate to the increase of Nedd4 and Itch proteins, pUL42 should affect these Nedd4 proteins to downregulate CD86.<\/jats:p>","DOI":"10.1111\/1348-0421.13176","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T07:14:38Z","timestamp":1728458078000},"page":"406-413","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Downregulation of CD86 in HCMV\u2010infected THP\u20101 cells"],"prefix":"10.1111","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2783-2520","authenticated-orcid":false,"given":"Tetsuo","family":"Koshizuka","sequence":"first","affiliation":[{"name":"Microbiology and Immunology Gifu Pharmaceutical University Gifu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuta","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Microbiology and Immunology Gifu Pharmaceutical University Gifu 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