Functional analysis of glycosylation of Zika virus envelope protein

Details

• Alternative Title:
  Cell Rep
• Personal Author:
  Fontes-Garfias, Camila R. ; Shan, Chao ; Luo, Huanle ; Muruato, Antonio E. ; Medeiros, Daniele B.A. ; Mays, Elizabeth ; Xie, Xuping ; Zou, Jing ; Roundy, Christopher M. ; Wakamiya, Maki ; Rossi, Shannan L. ; Wang, Tian ; Weaver, Scott C. ; Shi, Pei-Yong
• Description:
  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.
• Subjects:
  Aedes Animals Antibodies, Neutralizing Article Bone Marrow Cells Cells, Cultured Chlorocebus Aethiops Cytokines Dendritic Cells Flavivirus Entry Glycosylation Insect Vectors Mice Mosquito Transmission Protein Structure, Tertiary RNA, Viral Vaccine Vero Cells Viral Envelope Proteins Virulence Virus Assembly Virus Replication Zika Virus Zika Virus Infection

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• Source:
  Cell Rep. 21(5):1180-1190
• Pubmed ID:
  29091758
• Pubmed Central ID:
  PMC5708593
• Document Type:
  Journal Article
• Funding:
  R01 AI127744/AI/NIAID NIH HHSUnited States/ ; U01 CK000512/CK/NCEZID CDC HHSUnited States/ ; R24 AI120942/AI/NIAID NIH HHSUnited States/ ; R01 AI099123/AI/NIAID NIH HHSUnited States/ ; UL1 TR001439/TR/NCATS NIH HHSUnited States/
• Volume:
  21
• Issue:
  5
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:436f55c30452cc6b75c7675cbc7ea7aa78f1bc2208b3ba280d22c14cf6b86c70
• Download URL:
  https://stacks.cdc.gov/view/cdc/121443/cdc_121443_DS1.pdf
• File Type:
  [PDF - 1.06 MB ]