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Flaviviruses are among the most important emerging viruses known to man. They cause a variety of diseases including encephalitis and (hemorrhagic) fevers. Currently, there is no specific antiviral therapy available for the treatment of infections with flaviviruses. The availability of a convenient small animal model would be very useful for the study of strategies for the treatment or prevention of flavivirus infections. In this work we present new animal models for the study of (i) antiviral therapy against flavivirus infections in rodents, (ii) the biology of flaviviruses, in particular factors of neuroinvasion and vector specificity.