CD14 facilitates perinatal human cytomegalovirus infection in biliary epithelial cells via CD55

Liang Su; Yan Chen; Ming Fu; Hezhen Wang; Yanlu Tong; Zefeng Lin; Hongjiao Chen; Huiting Lin; Yi Chen; Bing Zhu; Sige Ma; Yiyi Xiao; Junyu Huang; Ziyang Zhao; Fenjie Li; Rongchen Ye; Hongguang Shi; Zhe Wang; Jixiao Zeng; Zhe Wen; Minhua Luo; Huimin Xia; Ruizhong Zhang

JHEP Reports (May 2024)

CD14 facilitates perinatal human cytomegalovirus infection in biliary epithelial cells via CD55

Liang Su,
Yan Chen,
Ming Fu,
Hezhen Wang,
Yanlu Tong,
Zefeng Lin,
Hongjiao Chen,
Huiting Lin,
Yi Chen,
Bing Zhu,
Sige Ma,
Yiyi Xiao,
Junyu Huang,
Ziyang Zhao,
Fenjie Li,
Rongchen Ye,
Hongguang Shi,
Zhe Wang,
Jixiao Zeng,
Zhe Wen,
Minhua Luo,
Huimin Xia,
Ruizhong Zhang

Affiliations

Liang Su: Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China; Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
Yan Chen: Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China; Faculty of Medicine, Macau University of Science and Technology, Macau SAR, China
Ming Fu: Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China; Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China
Hezhen Wang: Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Yanlu Tong: Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Zefeng Lin: Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Hongjiao Chen: Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Huiting Lin: Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Yi Chen: Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Bing Zhu: Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Sige Ma: Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Yiyi Xiao: Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Junyu Huang: Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Ziyang Zhao: Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Fenjie Li: Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Rongchen Ye: Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Hongguang Shi: Department of Pediatric Surgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Zhe Wang: Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Jixiao Zeng: Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Zhe Wen: Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Minhua Luo: Faculty of Medicine, Macau University of Science and Technology, Macau SAR, China
Huimin Xia: Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China; Corresponding authors. Addresses: Provincial Key Laboratory of Research in Structure Birth Defect Disease, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, No. 9, Jinshui Road, Guangzhou, 510623, Guangdong, China. Tel.: +86-20-3807 6560; Fax. +86-20-3807-6020
Ruizhong Zhang: Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China; Department of Pediatric Surgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Corresponding authors. Addresses: Provincial Key Laboratory of Research in Structure Birth Defect Disease, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, No. 9, Jinshui Road, Guangzhou, 510623, Guangdong, China. Tel.: +86-20-3807 6560; Fax. +86-20-3807-6020

Journal volume & issue: Vol. 6, no. 5
p. 101018

Abstract

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Background & Aims: A high human cytomegalovirus (HCMV) infection rate accompanied by an increased level of bile duct damage is observed in the perinatal period. The possible mechanism was investigated. Methods: A total of 1,120 HCMV-positive and 9,297 HCMV-negative children were recruited, and depending on age, their liver biochemistry profile was compared. Fetal and infant biliary epithelial cells (F-BECs and I-BECs, respectively) were infected with HCMV, and the differences in cells were revealed by proteomic analysis. Protein–protein interactions were examined by coimmunoprecipitation and mass spectrometry analyses. A murine cytomegalovirus (MCMV) infection model was established to assess treatment effects. Results: Perinatal HCMV infection significantly increased the level of bile duct damage. Neonatal BALB/c mice inoculated with MCMV showed obvious inflammation in the portal area with an abnormal bile duct structure. Proteomics analysis showed higher CD14 expression in F-BECs than in I-BECs. CD14 siRNA administration hindered HCMV infection, and CD14-knockout mice showed lower MCMV-induced bile duct damage. HCMV infection upregulated CD55 and poly ADP-ribose polymerase-1 (PARP-1) expression in F-BECs. Coimmunoprecipitation and mass spectrometry analyses revealed formation of the CD14–CD55 complex. siRNA-mediated inhibition of CD55 expression reduced sCD14-promoted HCMV replication in F-BECs. In MCMV-infected mice, anti-mouse CD14 antibody and PARP-1 inhibitor treatment diminished cell death, ameliorated bile duct damage, and reduced mortality. Conclusions: CD14 facilitates perinatal HCMV infection in BECs via CD55, and PARP-1-mediated cell death was detected in perinatal cytomegalovirus-infected BECs. These results provide new insight into the treatment of perinatal HCMV infection with bile duct damage. Impact and implications: Perinatal human cytomegalovirus (HCMV) infection is associated with bile duct damage, but the underlying mechanism is still unknown. We discovered that CD14 expression is increased in biliary epithelial cells during perinatal HCMV infection and facilitates viral entry through CD55. We also detected PARP-1-mediated cell death in perinatal HCMV-infected biliary epithelial cells. We showed that blocking CD14 or inhibiting PARP-1 reduced bile duct damage and mortality in a mouse model of murine cytomegalovirus infection. Our findings provide a new insight into therapeutic strategies for perinatal HCMV infection.

Published in JHEP Reports

ISSN: 2589-5559 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the digestive system. Gastroenterology
Website: https://www.journals.elsevier.com/jhep-reports

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