Attenuated West Nile virus mutant NS1_{130-132QQA/175A/207A} exhibits virus-induced ultrastructural changes and accumulation of protein in the endoplasmic reticulum

We have previously shown that ablation of the three N-linked glycosylation sites in the West Nile virus NS1 protein completely attenuates mouse neuroinvasiveness (≥ 1,000,000 PFU). Here, we compared the replication of the NS1_{130-132QQA/175A/207A} mutant to that of the parental NY99 strain in monkey kidney Vero cells. The results suggest that the mechanism of attenuation is a lack of NS1 glycosylation, which blocks efficient replication, maturation, and NS1 secretion from the endoplasmic reticulum and results in changes to the virus-induced ultrastructure.