Protein disulfide isomerases negatively regulate ebolavirus structural glycoprotein expression in the endoplasmic reticulum via the autophagy-lysosomal pathway

High level expression of ebolavirus glycoprotein (GP) alone triggers cell rounding, detachment and down-regulation of many cellular surface molecules, which is considered to be involved in viral pathogenesis. This report demonstrated that the protein disulfide isomerases (PDIs) plays an essential role for negatively regulating GP expression in the cells. A PDI protein PDIA3 triggers the GP misfolding, which is further degraded via autophagy lysosomal pathway. PDIA3 has been also shown to decrease the expression of GPs of other ebolaviruses, but not of Marburg virus, which is consistent with that the Marburg GP expression does not cause the cytopathic effect.