Claudin2 is involved in the interaction between Megalocytivirus-induced virus-mock basement membrane (VMBM) and
Jian-Hui He1,2, Deyu Han1,2, Xianyu Meng1,2
1State Key Laboratory of Biocontrol, School of Life Sciences/ Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai)/ China-ASEAN Belt and Road Joint Laboratory On Mariculture Technology, Sun Yat-Sen University, Guangzhou, China.
Abstract:
The genus Megalocytivirus, belonging to the family Iridoviridae, is one of the most detrimental virus groups to fish aquaculture. Megalocytivirus creates a virus-mock basement membrane (VMBM) on the surface of infected cells. This membrane provides attachment sites for lymphatic endothelial cells (LECs), disrupting fish's endothelial cell-extracellular matrix system. This disruption triggers injury to the vascular system and can result in death. Exploring the VMBM-cell interaction mechanism is crucial for uncovering the pathogenesis of Megalocytivirus and identifying therapeutic targets. Claudins, a class of tetra transmembrane proteins, play a key role in creating tight junctions between endothelial or epithelial cells. In this study, we demonstrated that the expression of Claudin2, a member of the Claudin family in fish, was significantly up-regulated by Megalocytivirus infection. Claudin2 was found in LECs attached to the surface of infected cells. It interacted with the VMBM viral components VP23R, VP08R, and VP33L at multiple binding sites through its two extracellular loops. However, it did not interact with the host basement membrane's nidogen. Therefore, Claudin2 is involved in the interaction of LEC with VMBM and plays a role in the disturbed distribution of extracellular matrix and endothelial cells in Megalocytivirus-infected fish tissues. This study aims to uncover the molecular mechanisms by which Megalocytivirus infection leads to pathological changes in the vascular system.
Insights
Megalocytivirus infection up-regulates Claudin2 in fish, enabling virus-mock basement membrane attachment to lymphatic endothelial cells. This interaction disrupts vascular integrity, contributing to fish disease pathogenesis.
Area of Science:
- Aquatic animal virology
- Cellular and molecular pathology
- Fish immunology
Background:
- Megalocytivirus causes significant losses in fish aquaculture.
- The virus forms a virus-mock basement membrane (VMBM) on infected cells, disrupting endothelial cell-extracellular matrix interactions.
- Understanding VMBM-cell interactions is key to revealing Megalocytivirus pathogenesis.
Purpose of the Study:
- To investigate the role of Claudin2 in the interaction between lymphatic endothelial cells (LECs) and the VMBM during Megalocytivirus infection.
- To elucidate the molecular mechanisms underlying vascular pathology in infected fish.
Main Methods:
- Analysis of Claudin2 expression in Megalocytivirus-infected fish tissues.
- Immunofluorescence microscopy to visualize Claudin2 localization and interaction with VMBM components.
- Co-immunoprecipitation assays to confirm binding interactions.
Main Results:
- Megalocytivirus infection significantly up-regulated Claudin2 expression in fish.
- Claudin2 was localized to LECs interacting with the VMBM on infected cells.
- Claudin2 directly interacted with viral proteins VP23R, VP08R, and VP33L via its extracellular loops, but not with host nidogen.
Conclusions:
- Claudin2 is a crucial mediator of LEC attachment to the VMBM in Megalocytivirus-infected fish.
- This interaction contributes to the disruption of vascular integrity and extracellular matrix distribution.
- Claudin2 represents a potential therapeutic target for mitigating Megalocytivirus-induced pathology.
