BoDV-1 Infection Is Associated with Altered Prion Protein Glycoform Maturation and Reduced ETS1-MGAT5/GnTV Pathway Activity in Rat C6 Astroglial Cells
TL;DR
It is suggested that persistent BoDV-1 infection may impair PrPC N-glycan maturation through suppression of the ETS1–MGAT5/GnTV pathway activity, thereby potentially affecting astroglial antioxidative capacity.
Abstract
Borna disease virus 1 (BoDV-1) is a noncytolytic, neurotrophic virus that causes neurological disorders, where astrocytes contribute to neuropathology. Cellular prion protein (PrPC) is involved in pro-survival signaling and antioxidative defense. Using rat astroglial C6 cells as an in vitro model, we investigated whether persistent BoDV-1 infection alters N-glycan maturation of PrPC. Western blotting showed that PrPC shifted toward lower-molecular-weight glycoforms as cell density increased. This tendency was more evident in BoDV-1-infected C6 cells without detectable changes in total surface PrPC expression. Two-dimensional polyacrylamide gel electrophoresis showed a shift of PrPC toward lower molecular weight and more basic isoelectric points. Conventional RT-PCR detected reduced signals of MGAT5, which encodes N-acetylglucosaminyltransferase V (GnTV), whereas MGAT1–4 signals were not markedly altered. In addition, GnTV overexpression induced a higher-molecular-weight shift of PrPC. PHA-L4 precipitation followed by anti-PrP immunoblotting showed reduced β1-6-branched complex N-glycan signals associated with PrPC. BoDV-1 infection also decreased the RT-PCR signal of E26 transformation-specific 1 (ETS1) as well as reduced ETS-dependent promoter activity and superoxide dismutase activity. These findings suggest that persistent BoDV-1 infection may impair PrPC N-glycan maturation through suppression of the ETS1–MGAT5/GnTV pathway activity, thereby potentially affecting astroglial antioxidative capacity.