Flaviviruses are enveloped viruses with a single-stranded, 10.7kb positive-sense 
RNA genome. The genomic RNA, which has a 5' cap but no poly(A) tail, is 
translated as a single polyprotein that is then cleaved into three structural 
proteins and seven non-structural (NS) proteins by both viral and host 
proteases. The NS proteins include an RNA-dependent RNA polymerase (NS5), a 
helicase/protease (NS3), and other proteins that form part of the viral 
replication complex. Sequences and structures in the 5' and 3' untranslated 
regions (UTR) and capsid gene, including the cyclization sequences, the upstream 
AUG region, and the terminal 3' stem-loop, regulate translation, RNA synthesis 
and viral replication. We have also found that an RNA hairpin structure in the 
capsid coding region (cHP) influences start codon selection and viral 
replication of the flavivirus dengue virus (DENV). Peptide-conjugated 
phosphorodiamidate morpholino oligomers (P-PMOs) were used to further dissect 
the role of conserved regions of the 5' and 3' UTRs; several P-PMOs were shown 
to specifically inhibit DENV translation and/or RNA synthesis and, hence, are 
potentially useful as antiviral agents. Regarding the mechanism of DENV 
translation, we have shown that DENV undergoes canonical cap-dependent 
translation initiation as well as a non-canonical mechanism when cap-dependent 
translation is suppressed. Although much remains to be elucidated about the 
molecular biology of flavivirus infection, progress is being made towards 
defining the cis and trans factors that regulate flavivirus translation and 
replication.