Whiteman Melissa C, Popov Vsevolod, Sherman Michael B, Wen Julie, Barrett Alan D T
Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA.
Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, USA.
J Virol. 2015 Jan 15;89(2):1474-8. doi: 10.1128/JVI.02215-14. Epub 2014 Nov 12.
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 NS1130-132QQA/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.
我们之前已经表明,西尼罗河病毒NS1蛋白中三个N-连接糖基化位点的缺失完全减弱了小鼠神经侵袭性(≥1,000,000 PFU)。在此,我们比较了NS1 130-132QQA/175A/207A突变体与亲本NY99株在猴肾Vero细胞中的复制情况。结果表明,减毒机制是NS1糖基化缺失,这会阻断内质网中高效的复制、成熟及NS1分泌,并导致病毒诱导的超微结构发生变化。