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
Affiliations
Camila R. Fontes-Garfias
Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA
Chao Shan
Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA
Huanle Luo
Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX, USA
Antonio E. Muruato
Institute for Human Infections & Immunity, University of Texas Medical Branch, Galveston, TX, USA; Institute for Translational Science, University of Texas Medical Branch, Galveston, TX, USA
Daniele B.A. Medeiros
Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA; Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil
Elizabeth Mays
Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX, USA
Xuping Xie
Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA
Jing Zou
Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA
Christopher M. Roundy
Institute for Human Infections & Immunity, University of Texas Medical Branch, Galveston, TX, USA; Institute for Translational Science, University of Texas Medical Branch, Galveston, TX, USA
Maki Wakamiya
Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA
Shannan L. Rossi
Institute for Human Infections & Immunity, University of Texas Medical Branch, Galveston, TX, USA; Department of Pathology and Center for Biodefense & Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX, USA
Tian Wang
Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX, USA; Department of Pathology and Center for Biodefense & Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX, USA; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, USA
Scott C. Weaver
Institute for Human Infections & Immunity, University of Texas Medical Branch, Galveston, TX, USA; Institute for Translational Science, University of Texas Medical Branch, Galveston, TX, USA; Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX, USA; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, USA; Sealy Center for Structural Biology & Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, USA
Pei-Yong Shi
Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, USA; Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, TX, USA; Sealy Center for Structural Biology & Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, USA; Corresponding author
Summary: 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. Keywords: Zika virus, glycosylation, flavivirus entry, mosquito transmission, vaccine
