Maki Wakamiya, Huanle Luo, Pei Yong Shi, Camila R. Fontes-Garfias, Shannan L. Rossi, Scott C. Weaver, Daniele Barbosa de Almeida Medeiros, Jing Zou, Antonio E. Muruato, Xuping Xie, Chao Shan, Tian Wang, Christopher M. Roundy, and Elizabeth Mays
University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA. University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA. University of Texas Medical Branch. Department of Microbiology & Immunology. Galveston, TX, USA. University of Texas Medical Branch. Institute for Human Infections & Immunity. Galveston, TX, USA / University of Texas Medical Branch. Institute for Translational Science. Galveston, TX, USA. University of Texas Medical Branch. Department of Microbiology & Immunology. Galveston, TX, USA / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. University of Texas Medical Branch. Department of Microbiology & Immunology. Galveston, TX, USA . University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA. University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA. University of Texas Medical Branch. Institute for Human Infections & Immunity. Galveston, TX, USA / University of Texas Medical Branch. Institute for Translational Science. Galveston, TX, USA. University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA. University of Texas Medical Branch. Institute for Human Infections & Immunity. Galveston, TX, USA / University of Texas Medical Branch. Department of Pathology and Center for Biodefense & Emerging Infectious Diseases. Galveston, TX, USA. University of Texas Medical Branch. Department of Microbiology & Immunology. Galveston, TX, USA / University of Texas Medical Branch. Department of Pathology and Center for Biodefense & Emerging Infectious Diseases. Galveston, TX, USA / University of Texas Medical Branch. Sealy Center for Vaccine Development. Galveston, TX, USA. University of Texas Medical Branch. Institute for Human Infections & Immunity. Galveston, TX, USA / University of Texas Medical Branch. Institute for Translational Science. Galveston, TX, USA / University of Texas Medical Branch. Department of Microbiology & Immunology. Galveston, TX, USA / University of Texas Medical Branch. Sealy Center for Vaccine Development. Galveston, TX, USA / University of Texas Medical Branch. Sealy Center for Structural Biology & Molecular Biophysics. Galveston, TX, USA. University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA / University of Texas Medical Branch. Sealy Center for Vaccine Development. Galveston, TX, USA / University of Texas Medical Branch. Department of Pharmacology & Toxicology. Galveston, TX, USA / University of Texas Medical Branch. Sealy Center for Structural Biology & Molecular Biophysics. Galveston, TX, USA. 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.