Molecular mechanism of the interaction between Megalocytivirus-induced virus-mock basement membrane (VMBM) and lymphatic endothelial cells.

The Megalocytivirus genus, family Iridoviridae, is a group of large DNA viruses that pose significant threats to marine and freshwater fishes. In tissues, the Megalocytivirus-infected cells are attached by a layer of lymphatic endothelial cells (LECs), constituting a unique histopathological phenomenon. Megalocytivirus induces the formation of an extracellular structure on the surface of infected cells that is functionally similar to the host basement membrane (BM), known as the virus-mock basement membrane (VMBM). VMBM is composed of host BM component nidogen-1 and viral proteins VP23R and VP08R and specifically provides adhesive support for LECs. In the current study, the viral protein VP33L was identified as a novel component of VMBM, and the way it participates in VMBM assembly was investigated. The interactions between virus-encoded VMBM components and LEC-specific markers lymphatic vessel endothelial receptor-1 (LYVE-1) and vascular endothelial growth factor receptor 3 (VEGFR-3), which contribute to the selective adhesion of LECs on VMBM, were further analyzed. Moreover, the viral components of VMBM could regulate the proliferation and migration of LECs via the VEGFR-3 signaling, which partially explains the origin of LECs attached to infected cells. This study is important for revealing the pathogenesis of Megalocytivirus and potentially provides reference clues for exploring the interaction mechanism between endothelial cells and extracellular matrix in animals. [ABSTRACT FROM AUTHOR]