Structural and molecular basis for foot-and-mouth disease virus neutralization by two potent protective antibodies

Figures

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  Figure 1. Characterizations of anti-FMDV NAbs M8 and M170. (A) BIAcore SPR kinetic profile of mAb M8 (top) and M170 (bottom) against FMDV O. The binding affinity is depicted by KD (equilibrium dissociation constant, KD = Kd/Ka), which was calculated by the BIAcore 3000 analysis software (BIAevaluation version 4.1). (B) Analysis of the simultaneous binding of M8 and M170 to FMDV through a competitive SPR assay. Due to the requirement of acidic condition for the sensor-labeling, M8 or M170, rather than FMDV, was loaded onto the sensor. In the upper panel, the sensor was labeled with M8. FMDV was inject first, followed by the second injection of M8 again to fully occupy all binding sites for M8 on viral surface, then M170 flowed through. In the bottom panel, the sensor was labeled with M170. The SPR procedure of M170 is same to that of M8. Note: signals (during 800–1000 s) decreased upon M8 binding in the bottom panel, which might result from the ability that M8 has the potential to strip FMDV off the M170-labelled sensor due to the higher binding affinity. (C) Neutralization of FMDV O by M8/M170 (top) and the combination of M8 and M170 (bottom) using plaque-reduction neutralization assay.…

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  Figure 2. Cryo-EM structures, mechanism of neutralization of FMDV by M8 or M170. (A) Cryo-EM maps of FMDV-M8-complex (left) and FMDV-M170-complex (right). The viral capsids of both complexes are rainbow-colored as the color bar shown below; the M8 and M170 are colored in cyan and magenta, respectively. (B) Electron density maps for the binding interface of M8 and one protomer of the FMDV capsid. The inset shows the density maps and atomic model of VP1 GH loop. Residues with side chains are labeled. Surface representation (left) and epitopes (right) of M8 (C) and M170 (D) on a viral pentamer. The pentamers are shown as surface (left) or cartoon (right) in the signature colors (VP1, blue; VP2, green; VP3, red), while M8 and M170 are colored in the same scheme as in Fig. 2A. The epitopes of M8 (right in 2C) and M170 (right in 2D) are shown as spheres and those from one protomeric unit are circled by black dotted lines. (E) The structural basis of M8 (left) and M170 (right) binding to FMDV. Loops from FMDV involved in interactions with M8/M170 are shown as cartoon, while the remaining parts are shown as surface. M8 and M170 are represented as cartoon. The color scheme is as in Fig. 2A. (F)…