Dengue virus host protein-RNA interactions

Dengue fever is the most important arthropod-transmitted disease worldwide, with millions of people infected or at risk. Consistent with our overall goal of understanding viral RNA-protein complexes and translation of non-adenylated viral mRNAs, we have identified several proteins that bind specifically to the 3’ terminus of dengue fever virus RNA. The 3’ termini of flavivirus RNAs (i.e. the family that includes dengue fever virus, West Nile virus, and Japanese encephalitis virus) have a conserved folding pattern; therefore, we hypothesize that there is overlap among the sets of proteins binding to the different viral RNAs.

Several proteins, including NF90 and RNA helicase A bind specifically to the 3' -terminal stem-loop structure of the dengue virus RNA (Gomila, Martin, and Gehrke, in preparation). Upon dengue virus infection, the NF90 protein translocates into the nucleus; however, RHA does not follow the same pattern. The functions of the proteins are being tested by siRNA knockdowns. NF90 has been reported to regulate the stability of RNAs containing AUUUA repeats in the 3' UTR (Vumbaca, F., K. N. Phoenix, D. Rodriguez-Pinto, D. K. Han, and K. P. Claffey. 2008. Double-stranded RNA-binding protein regulates vascular endothelial growth factor mRNA stability, translation, and breast cancer angiogenesis. Mol Cell Biol 28:772-83). Knockdown of NF90 protein is accompanied by a significant decrease in dengue virus repication, suggesting that it is a positive determinant of dengue virus replication.