This study was carried out following strict guidelines from the care and use manual of National Laboratory Animal Center. The protocol was approved by the Committee on the Ethics of Animal Experiments of Academia Sinica. (Permit Number: MMi-ZOOWH2009102). The mice were killed with 50% CO 2 containing 50% O 2 . All efforts were made to minimize suffering. (i) Breeder mice of the ICR strain were purchased from the Laboratory Animal Center National Taiwan University College of Medicine. Purified mAbs at doses of 1, 10 and 100 mg/ml were incubated with 1610 4 pfu (25-fold LD 50 ) of DENV-2 (16681) at 4uC for 30 mins. Two-day-old suckling mouse brain was inoculated with 20 ml of the reaction mixture by intracranial (i.c.) injection. Survival rate and signs of illness, including paralysis, were observed daily for 21 days following challenge. In post-exposure therapeutic experiments, mice were passively injected with 5 mg of mAb via i.c. route after 1 day of infection. (ii) Stat1-deficient mice (Stat1 2/2 ) [31] were bred in the specific-pathogen-free animal facility at the Institute of Biomedical Sciences, Academia Sinica. Mice were challenged intraperitoneally with 1610 5 pfu (300-fold LD 50 ) of DENV-2 (NGC-N) in 300 ml of PBS and simultaneously injected intracranially (i.c.) with 30 ml of PBS. In prophylaxis experiments, antibodies (100 mg per mouse, intraperitoneally) were administered 1 day before infection and administered on day 0, 1, 3, 5 and 7 after infection. In postexposure therapeutic experiments, antibodies (100 mg per mouse, intraperitoneally) were administered on day 1, 3, 5 and 7 after infection.