Figure 5.

Model for 3C N69D-mediated attenuation of EV71 virulence. The N69D substitution of 3C^pro decreases viral reproductivity due to a slower processing rate of viral precursor polypeptides. The N69D mutation can also affect the ability of 3C^pro to promote the shutoff of host cell metabolism by hydrolysis of CstF-64 and other factors. Most importantly, this substitution weakens the inhibition of host immune system mediated by protease activity of 3C by hydrolysis of IRF-7 and inhibition of NF-κB pathway. Taken together, the 3C N69D mutation was responsible for the attenuation of EV71 virulence.