Development of a nonhuman primate model for dengue virus infection

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To develop a nonhuman primate model for dengue virus (DV) infection, rhesus monkeys were inoculated with DV types 1 and 2. The DV types 1 and 2 induced viremia with duration from 2 to 3 days and a mean peak titer of 4×10^3 RNA copies/ml but infected monkeys showed no sign of dengue diseases even after inoculation of high virus doses. DV type 2 effectively replicates in MDM cells derived from bonnet monkeys compared to those derived from rhesus monkeys. These results suggest that bonnet monkey may be a useful model to study dengue disease.To improve a reverse genetics for tick-borne encephalitis virus (TBEV) which belongs to the same member of the Flavivirus genus as DV, we have constructed a plasmid-based infectious clone encoding full-length TBEV cDNA under control of the minimum cytomegalovirus promoter. Transfection of cells with the plasmid resulted in the production of infectious TBEV at high levels. Furthermore, we have developed homologous recombination-based reverse genetics for TBEV and DV. The reverse genetics approaches described here can be exploited for studies of DV replication and pathogenesis as powerful tools.