BHK-21 cells were grown at 37uC with 5% CO 2 in Minimal Essential Medium (MEM, Gibco) supplemented with 10% heatinactivated fetal bovine serum (FBS, Gibco) and 100 U/ml penicillin, 100 mg/ml streptomycin, 0.25 mg/ml amphotericin B (Antibiotic-Antimycotic, Gibco). Aedes albopictus C6/36 cells were grown at 28uC in 1:1 Mitsuhashi and Maramorosch (MM) insect medium (Sigma-Aldrich)/Dulbecco's modified Eagle's medium (DMEM, Gibco) containing 10% FBS and 100 U/ml penicillin, 100 mg/ml streptomycin, 0.25 mg/ml amphotericin B (Antibiotic-Antimycotic, Gibco). The four DENVs (DENV-1 Hawaii, DENV-2 16681, DENV-3 H87 and DENV-4 H241) were provided by Dr. Duane J. Gubler from the Centers for Disease Control and Prevention, Fort Collins, U.S.A. The various DENV-2 strains including New Guinea-C (NGC), NGC-N (mouse-adapted neurovirulent), PL046 and Malaysia 07587 were used in this study [26, 27] . These viruses were passaged in C6/36 cells.