FIG. 1.

Schematic model of the flavivirus fusion process (A to E) and ribbon diagrams of the sE prefusion dimer (F and G) and postfusion trimer (H) of TBEV. E protein DI, red; E DII, yellow; E DIII, blue; FP, orange; stem, purple; transmembrane anchor, green; viral membrane, blue; target membrane, gray. (A) Metastable E dimer on the surface of native virions. (B) Low pH-induced dissociation of the dimer and insertion of the FP into the target membrane. (C) Relocation of DIII leading to hairpin formation, trimerization, and “zippering” of the stem along the body of the trimer. (D) Hemifusion intermediate. Only the contacting membrane leaflets are fused. (E) Fusion pore formation. In the final postfusion conformation, the FPs and the membrane anchors are juxtaposed in the fused membrane. (F) Side view and (G) top view of the sE dimer. (H) Side view of the sE trimer. The gray balls show the positions of mutations that affected binding of MAbs. The position of the carboxy terminus of sE is indicated by a purple arrow and labeled COO−.