Functional Analysis of Glycosylation of Zika Virus Envelope Protein

被引:122
作者
Fontes-Garfias, Camila R. [1 ]
Shan, Chao [1 ]
Luo, Huanle [5 ]
Muruato, Antonio E. [2 ,3 ]
Medeiros, Daniele B. A. [1 ,4 ]
Mays, Elizabeth [5 ]
Xie, Xuping [1 ]
Zou, Jing [1 ]
Roundy, Christopher M. [2 ,3 ]
Wakamiya, Maki [1 ]
Rossi, Shannan L. [2 ,6 ,7 ]
Wang, Tian [5 ,6 ,7 ,8 ]
Weaver, Scott C. [2 ,3 ,5 ,10 ]
Shi, Pei-Yong [1 ,8 ,9 ,10 ]
机构
[1] Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA
[2] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA
[3] Univ Texas Med Branch, Inst Translat Sci, Galveston, TX 77555 USA
[4] Minist Hlth, Evandro Chagas Inst, Dept Arbovirol & Hemorrhag Fevers, Ananindeua, Para, Brazil
[5] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA
[6] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA
[7] Univ Texas Med Branch, Ctr Biodefense & Emerging Infect Dis, Galveston, TX 77555 USA
[8] Univ Texas Med Branch, Sealy Ctr Vaccine Dev, Galveston, TX 77555 USA
[9] Univ Texas Med Branch, Dept Pharmacol & Toxicol, Galveston, TX 77555 USA
[10] Univ Texas Med Branch, Sealy Ctr Struct Biol & Mol Biophys, Galveston, TX 77555 USA
来源
CELL REPORTS | 2017年 / 21卷 / 05期
关键词
WEST-NILE-VIRUS; DENGUE-VIRUS; DC-SIGN; IN-VITRO; INFECTION; VACCINE; HETEROGENEITY; ENCEPHALITIS; MOSQUITOS; SEQUENCE;
D O I
10.1016/j.celrep.2017.10.016
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Zika virus (ZIKV) infection causes devastating congenital abnormities and Guillain-Barre syndrome. The ZIKV envelope (E) protein is responsible for viral entry and represents a major determinant for viral pathogenesis. Like other flaviviruses, the ZIKV E protein is glycosylated at amino acid N154. To study the function of E glycosylation, we generated a recombinant N154Q ZIKV that lacks the E glycosylation and analyzed the mutant virus in mammalian and mosquito hosts. In mouse models, the mutant was attenuated, as evidenced by lower viremia, decreased weight loss, and no mortality; however, knockout of E glycosylation did not significantly affect neurovirulence. Mice immunized with the mutant virus developed a robust neutralizing antibody response and were completely protected from wild-type ZIKV challenge. In mosquitoes, the mutant virus exhibited diminished oral infectivity for the Aedes aegypti vector. Collectively, the results demonstrate that E glycosylation is critical for ZIKV infection of mammalian and mosquito hosts.
引用
收藏
页码:1180 / 1190
页数:11
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