Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers

• Autores: Guntur Fibriansah, Kristie D. Ibarra, Thiam-Seng Ng
• Localización: Science, ISSN 0036-8075, Vol. 349, Nº 6243, 2015, págs. 88-91
• Idioma: inglés
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• Resumen

  • There are four closely-related dengue virus (DENV) serotypes. Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection. We demonstrated that DENV serotype 2 (DENV2)–specific human monoclonal antibody (HMAb) 2D22 is therapeutic in a mouse model of antibody-enhanced severe dengue disease. We determined the cryo–electron microscopy (cryo-EM) structures of HMAb 2D22 complexed with two different DENV2 strains. HMAb 2D22 binds across viral envelope (E) proteins in the dimeric structure, which probably blocks the E protein reorganization required for virus fusion. HMAb 2D22 “locks” two-thirds of or all dimers on the virus surface, depending on the strain, but neutralizes these DENV2 strains with equal potency. The epitope defined by HMAb 2D22 is a potential target for vaccines and therapeutics.