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Use of cryo-EM is examine HA head-directed monoclonal antibodies and influenza virus

July 05, 2019

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There has recently been growing interest in isolating and characterising potent neutralising antibodies that target the haemagglutinin (HA) of influenza viruses for use in both pandemics and epidemics. The authors used cryo-electron microscopy (cryoEM) to examine the mechanism of action of a potent HA head-directed monoclonal antibody (mAb) that is bound to influenza H7. They found that the epitope of the antibody is not solvent accessible in the compact, pre-fusion conformation that typifies all HA structures to date. Instead, the antibody binds between the HA head protomers, to an epitope that must be partly or transiently exposed in the pre-fusion conformation. The “breathing” of the HA protomers then occurs through the exposure of this epitope, which is consistent with the metastability of class I fusion proteins. Therefore this represents an early structural intermediate in the viral fusion process. Further work needs to occur to fully understand the extent of this transient exposure of conserved neutralising epitopes.

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Turner HL, Pallesen J, Lang S, Bangaru S, Urata S, et al. ISSN: PLoS Biol; 17(2): e3000139

2019

Added: July 05, 2019