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Role of BC loop residues in structure, function and antigenicity of the West Nile virus envelope protein receptor-binding domain III |
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| Authors: | Shuliu Zhang Rodrigo Maillard Gregory D. Gromowski David E. Volk Catherine H. Schein Claire Y.-H. Huang James C. Lee Alan D.T. Barrett David W.C. Beasley |
| Affiliation: | a Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA b Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA c Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA d Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX, USA e Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, USA f Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, USA g Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA h Arboviral Diseases Branch, Division of Vector-Borne Infectious Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases, Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Fort Collins, CO, USA. |
| Abstract: | Site-directed mutagenesis of residues in the BC loop (residues 329-333) of the envelope (E) protein domain III in a West Nile virus (WNV) infectious clone and in plasmids encoding recombinant WNV and dengue type 2 virus domain III proteins demonstrated a critical role for residues in this loop in the function and antigenicity of the E protein. This included a strict requirement for the tyrosine at residue 329 of WNV for virus viability and E domain III folding. The absence of an equivalent residue in this region of yellow fever group viruses and most tick-borne flavivirus suggests there is an evolutionary divergence in the molecular mechanisms of domain III folding employed by different flaviviruses. |
| Keywords: | Flavivirus West Nile virus Envelope protein Receptor binding domain Neutralization Attenuation |
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