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CD14 facilitates perinatal human cytomegalovirus infection in biliary epithelial cells via CD55.
Su, Liang; Chen, Yan; Fu, Ming; Wang, Hezhen; Tong, Yanlu; Lin, Zefeng; Chen, Hongjiao; Lin, Huiting; Chen, Yi; Zhu, Bing; Ma, Sige; Xiao, Yiyi; Huang, Junyu; Zhao, Ziyang; Li, Fenjie; Ye, Rongchen; Shi, Hongguang; Wang, Zhe; Zeng, Jixiao; Wen, Zhe; Luo, Minhua; Xia, Huimin; Zhang, Ruizhong.
Afiliación
  • Su L; 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.
  • Chen Y; Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
  • Fu M; 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.
  • Wang H; Faculty of Medicine, Macau University of Science and Technology, Macau SAR, China.
  • Tong Y; 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.
  • Lin Z; Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
  • Chen H; 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.
  • Lin H; 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.
  • Chen Y; 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.
  • Zhu B; 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.
  • Ma S; 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.
  • Xiao Y; 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.
  • Huang J; 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.
  • Zhao Z; 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.
  • Li F; 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.
  • Ye R; 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.
  • Shi H; 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.
  • Wang Z; 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.
  • Zeng J; 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.
  • Wen Z; Department of Pediatric Surgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • Luo M; 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.
  • Xia H; 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.
  • Zhang R; 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.
JHEP Rep ; 6(5): 101018, 2024 May.
Article en En | MEDLINE | ID: mdl-38601478
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: JHEP Rep Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: JHEP Rep Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos