In vivo adaptation of ZIKV clinical isolate SW01 increases virus virulence. A Schema of ZIKV in vivo passaging model; homogenate supernatant of infected mouse brain at 8 dpi was collected and used for the next round infection in naïve DP2 BALB/c mice. This process was repeated for 11 rounds to obtain a mouse adaptive virus MA-SW01. B–D DP2 BALB/c mice were injected i.c. with 100 PFU SW01, MA-SW01, or PBS (n=9–10 for each group). B Survival was monitored from 0 to 25 days post infection; C–D The morbidity of SW01 and MA-SW01 infected mice (clinical score: 0-healthy, 1-manic and limb weakness, 2-limb paralysis, 3-moribund or death); Survival rate were analyzed by log rank test; P values were indicated by ∗∗∗ (P < 0.001). Data shown are representative of two independent experiments.