Human cytomegalovirus UL23 inhibits immune cell migration and blocks antiviral immune cell responses by reducing the expression of chemokines CCL2 and CCL5

Human cytomegalovirus (HCMV) is a typical opportunistic human pathogen, which can endanger the lives of individuals with immune insufficiency or low immune function. One of the most effective immune mechanisms against HCMV in host cells is the production of antiviral cytokines. Chemokines are small...

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Main Authors: Hankun Wang, Chunling Zhang, Moran Li, Wangchun Zhao, Jialin Wang, Yanhong Ran, Xiaoping Yang, Zemin Deng, Jun Chen, Hongjian Li
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Virulence
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Online Access:https://www.tandfonline.com/doi/10.1080/21505594.2025.2500493
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author Hankun Wang
Chunling Zhang
Moran Li
Wangchun Zhao
Jialin Wang
Yanhong Ran
Xiaoping Yang
Zemin Deng
Jun Chen
Hongjian Li
author_facet Hankun Wang
Chunling Zhang
Moran Li
Wangchun Zhao
Jialin Wang
Yanhong Ran
Xiaoping Yang
Zemin Deng
Jun Chen
Hongjian Li
author_sort Hankun Wang
collection DOAJ
description Human cytomegalovirus (HCMV) is a typical opportunistic human pathogen, which can endanger the lives of individuals with immune insufficiency or low immune function. One of the most effective immune mechanisms against HCMV in host cells is the production of antiviral cytokines. Chemokines are small secreted proteins produced by cell immune responses to inflammatory stimuli or viral infection and act as potent chemoattractants for granulocytes, monocytes, lymphocytes and other leukocytes, and thus play a significant role in antiviral defence. Viruses have also evolved multiple strategies to resist the host’s immune system while coexisting with the host. In this study, based on RNA sequencing transcriptome differential analysis, we found that HCMV encoded UL23 May specifically down-regulate chemokines Chemokine ligand 2 (CCL2) and Chemokine ligand 5 (CCL5). Next, we determined that UL23 could inhibit the expression of Chemokine CCL2 and CCL5 by mainly affecting the phosphorylation of IRF-3, and then inhibited the migration of immune cells and blocked the antiviral immune responses in the migration and co-culture assays of HCMV-infected cells with immune migration-related cells. In conclusion, these results highlight that UL23 plays an important role in the immune evasion of HCMV by specially inhibiting the expression of chemokines CCL2 and CCL5, impairing the recruitment of immune cells by infected host cells and helping the virus escape immune killing.
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spelling doaj-art-2870a2ac1b124fc7af1bcc52b845e0402025-08-20T02:40:21ZengTaylor & Francis GroupVirulence2150-55942150-56082025-12-0116110.1080/21505594.2025.2500493Human cytomegalovirus UL23 inhibits immune cell migration and blocks antiviral immune cell responses by reducing the expression of chemokines CCL2 and CCL5Hankun Wang0Chunling Zhang1Moran Li2Wangchun Zhao3Jialin Wang4Yanhong Ran5Xiaoping Yang6Zemin Deng7Jun Chen8Hongjian Li9State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, ChinaState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, ChinaDepartment of Biotechnology, College of Life Science and Technology, Jinan University, Guangzhou, ChinaDepartment of Biotechnology, College of Life Science and Technology, Jinan University, Guangzhou, ChinaDepartment of Biotechnology, College of Life Science and Technology, Jinan University, Guangzhou, ChinaDepartment of Biotechnology, College of Life Science and Technology, Jinan University, Guangzhou, ChinaDepartment of Biotechnology, College of Life Science and Technology, Jinan University, Guangzhou, ChinaState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, ChinaState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, ChinaState Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, ChinaHuman cytomegalovirus (HCMV) is a typical opportunistic human pathogen, which can endanger the lives of individuals with immune insufficiency or low immune function. One of the most effective immune mechanisms against HCMV in host cells is the production of antiviral cytokines. Chemokines are small secreted proteins produced by cell immune responses to inflammatory stimuli or viral infection and act as potent chemoattractants for granulocytes, monocytes, lymphocytes and other leukocytes, and thus play a significant role in antiviral defence. Viruses have also evolved multiple strategies to resist the host’s immune system while coexisting with the host. In this study, based on RNA sequencing transcriptome differential analysis, we found that HCMV encoded UL23 May specifically down-regulate chemokines Chemokine ligand 2 (CCL2) and Chemokine ligand 5 (CCL5). Next, we determined that UL23 could inhibit the expression of Chemokine CCL2 and CCL5 by mainly affecting the phosphorylation of IRF-3, and then inhibited the migration of immune cells and blocked the antiviral immune responses in the migration and co-culture assays of HCMV-infected cells with immune migration-related cells. In conclusion, these results highlight that UL23 plays an important role in the immune evasion of HCMV by specially inhibiting the expression of chemokines CCL2 and CCL5, impairing the recruitment of immune cells by infected host cells and helping the virus escape immune killing.https://www.tandfonline.com/doi/10.1080/21505594.2025.2500493Human cytomegalovirus, HCMVUL23chemokine ligand 2, CCL2chemokine ligand 5, CCL5
spellingShingle Hankun Wang
Chunling Zhang
Moran Li
Wangchun Zhao
Jialin Wang
Yanhong Ran
Xiaoping Yang
Zemin Deng
Jun Chen
Hongjian Li
Human cytomegalovirus UL23 inhibits immune cell migration and blocks antiviral immune cell responses by reducing the expression of chemokines CCL2 and CCL5
Virulence
Human cytomegalovirus, HCMV
UL23
chemokine ligand 2, CCL2
chemokine ligand 5, CCL5
title Human cytomegalovirus UL23 inhibits immune cell migration and blocks antiviral immune cell responses by reducing the expression of chemokines CCL2 and CCL5
title_full Human cytomegalovirus UL23 inhibits immune cell migration and blocks antiviral immune cell responses by reducing the expression of chemokines CCL2 and CCL5
title_fullStr Human cytomegalovirus UL23 inhibits immune cell migration and blocks antiviral immune cell responses by reducing the expression of chemokines CCL2 and CCL5
title_full_unstemmed Human cytomegalovirus UL23 inhibits immune cell migration and blocks antiviral immune cell responses by reducing the expression of chemokines CCL2 and CCL5
title_short Human cytomegalovirus UL23 inhibits immune cell migration and blocks antiviral immune cell responses by reducing the expression of chemokines CCL2 and CCL5
title_sort human cytomegalovirus ul23 inhibits immune cell migration and blocks antiviral immune cell responses by reducing the expression of chemokines ccl2 and ccl5
topic Human cytomegalovirus, HCMV
UL23
chemokine ligand 2, CCL2
chemokine ligand 5, CCL5
url https://www.tandfonline.com/doi/10.1080/21505594.2025.2500493
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