High reduced/oxidized glutathione ratio in infectious spleen and kidney necrosis virus-infected cells contributes to degradation of VP08R multimers

Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus, family Iridoviridae. The ISKNV-infected cells in fish tissues are attached by lymphatic endothelial cells (LECs), which is a unique pathological phenomenon of ISKNV infection. The viral proteins VP23R and VP08R and the host protein nidogen-1 constitute the virus-mock basement membrane (VMBM) on the membrane of infected cells to provide attaching sites for LECs. VP08R can form cross-linked multimers via intermolecular disulfide bonds to make VMBM a compact and strong structure. A question is that when the virions mature, how do they penetrate VMBMs to be released from the cells? In this study, the redox state in ISKNV-infected cells was investigated. We demonstrated that the ratio of reduced/oxidized glutathione (GSH/GSSG) was significantly elevated in ISKNV-infected cells, suggesting the increasing of reducing power. Remarkable changes were also observed in activities of many GSH metabolic enzymes and in the ratio of NADPH/NADP. We further exhibited that the high ratio of GSH/GSSG could lead to degradation of the VP08R multimer in vitro. These may suggest that the high GSH/GSSG ratio in infected cells could act on the VP08R multimer to facilitate the disassembly of VMBMs after virus maturation.