Functional Analysis of Glycosylation of Zika Virus Envelope Protein

Camila R. Fontes-Garfias, Chao Shan, Huanle Luo, Antonio E. Muruato, Daniele B.A. Medeiros, Elizabeth Mays, Xuping Xie, Jing Zou, Christopher M. Roundy, Maki Wakamiya, Shannan L. Rossi, Tian Wang, Scott C. Weaver, Pei Yong Shi

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

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. Zika virus (ZIKV) causes devastating congenital abnormities and Guillain-Barré syndrome. Fontes-Garfias et al. showed that the glycosylation of ZIKV envelope protein plays an important role in infecting mosquito vectors and pathogenesis in mouse.

Original languageEnglish (US)
Pages (from-to)1180-1190
Number of pages11
JournalCell Reports
Volume21
Issue number5
DOIs
StatePublished - Oct 31 2017

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Keywords

  • Zika virus
  • flavivirus entry
  • glycosylation
  • mosquito transmission
  • vaccine

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Fontes-Garfias, C. R., Shan, C., Luo, H., Muruato, A. E., Medeiros, D. B. A., Mays, E., Xie, X., Zou, J., Roundy, C. M., Wakamiya, M., Rossi, S. L., Wang, T., Weaver, S. C., & Shi, P. Y. (2017). Functional Analysis of Glycosylation of Zika Virus Envelope Protein. Cell Reports, 21(5), 1180-1190. https://doi.org/10.1016/j.celrep.2017.10.016