Functional Analysis of Glycosylation of Zika Virus Envelope Protein

• DOI: 10.1016/j.celrep.2017.10.016
• Publication Date: 2017-10-31T15:47:37Z
• Authors: Camila R. Fontes-...; Chao Shan; Huanle Luo; Antonio E. Muruato; Daniele B.A. Mede...; Elizabeth Mays; Xuping Xie; Jing Zou; Christopher M. Ro...; Maki Wakamiya; Shannan L. Rossi; Tian Wang; Scott C. Weaver; Pei-Yong Shi
• Keywords: 0301 basic medicine; Glycosylation; QH301-705.5; Bone Marrow Cells; Virus Replication; Mice; 03 medical and health sciences; Viral Envelope Proteins; Aedes; Chlorocebus aethiops; Animals; Biology (General); Vero Cells; Cells, Cultured; Virulence; Zika Virus Infection; Virus Assembly; Dendritic Cells; Zika Virus; Antibodies, Neutralizing; Insect Vectors; Protein Structure, Tertiary; 3. Good health; Cytokines; RNA, Viral

Zika virus (ZIKV) infection causes devastating congenital abnormities and Guillain-Barré 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.