We downloaded the crystal structures of immature E (PDB id: 6lnu) and mature E (PDB id: 5ire) from the PDB database. The position of NGF on the two crystal structures of E is manually compared (Figure ). As illustrated in Figure , Zika E (in the endosome) is already a trimer and has taken on the structural characteristice. Figure .A demonstrates that immature E possesses the NGF A-B domain. As illustrated in Figure .B, mature E possesses only the NGF B domain. It indicates that NGF A has been depleted during the immature-to-mature transition of E. The protease furin may be used to achieve this operation of cutting. Zika E contains only six cysteines in the NGF A domain, which possess NGF activity. The NGF/TrkA endosomal signal can originate from the dendrites or soma of neurons. If Zika Virus lacks a regulatory mechanism, the E/TrkA-derived NGF/TrkA-like endosome signal may cause the virus-carrying endosome to travel back and forth between the soma and dendrites. It is not effective to Zika infection. Zika E matures in the low pH environment of the endosome after the host protease furin cleaves prM to reveal the fusion loop . It means that when the endosome containing Zika reaches the soma, the NGF domain of E loses its function owing to the endosome's acidic environment and is cut off by the protease furin. As a result, the mature E protein of Zika lacks NGF action, but the immature E protein does.