The instant invention provides stable and novel lineage I WNV reverse
genetics systems, and methods for making the reverse genetics systems,
specifically, a fully-infectious lineage I WNV cDNA or replicon system
engineered with one or more nucleotide sequences each encoding a reporter
gene to be used in high throughput cell-based screening assays for the
identification of novel antiflaviviral chemotherapeutics and/or vaccines
effective to treat and/or immunize against infections by WNV and other
emerging flaviviruses, such as, for example, JEV, SLEV, AV, KV, JV, CV,
YV, TBEV, DENV-1, DENV-2, DENV-3, DENV-4, YFV and MVEV. The present
invention further provides methods of high throughput screening of
antiflaviviral compounds or improved derivatives thereof using novel
lineage I WNV reverse genetics systems and/or cell lines stably
containing the reverse genetics systems. Also, the invention provides
novel pharmaceutical compositions comprising an attenuated lineage I WNV
that is less virulent but similarly immunogenic as the parent WNV and is
capable of providing a protective immune response in a host.