Partial glycosylation of the Ibaraki virus NS3 protein is sufficient to support virus propagation

Abstract

Ibaraki virus (IBAV) causes Ibaraki disease. We have previously shown that IBAV NS3 protein is highly glycosylated and that tunicamycin, an inhibitor of N-linked glycosylation, suppressed NS3 glycosylation and viral propagation. Since tunicamycin is known to cause endoplasmic reticulum (ER) stress, we explored the effects of ER stress and NS3 glycosylation on IBAV infection using tunicamycin and thapsigargin. These reagents both induced ER stress and NS3 glycosylation inhibition in a concentration-dependent manner, and as in our previous report, high concentrations of tunicamycin and thapsigargin suppressed IBAV propagation. However, lower concentrations of these reagents produced limited differences in IBAV propagation, despite their ability to suppress NS3 glycosylation and induce ER stress. These findings suggest that a considerable degree of NS3 glycosylation inhibition and ER stress induction does not suppress IBAV propagation. Conversely, lower concentrations of thapsigargin enhanced IBAV propagation, suggesting that moderate ER stress could benefit IBAV.