Attenuated West Nile Virus Mutant NS1130-132QQA/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.