Immunostimulatory sequence-specific RNA oligonucleotides corresponding to 3'terminal sequences of single-stranded minus-sense RNA genomic RNAs areprovided. Also provided are compositions and methods relating to animmunostimulatory 4-mer RNA motif provided as 5'-C/U-U-G/U-U-3'. Incorporationof this short RNA motif is sufficient to confer new and alteredimmunostimulatory properties in new and existing oligonucleotides, includingCpG oligodeoxynucleotides. Also provided are methods for use of theimmunostimulatory RNA oligonucleotides and DNA:RNA chimeric oligonucleotidesof the invention to induce an immune response in vitro and in vivo, as well asto treat allergy, asthma, infection, and cancer in a subject. Single-strandedoligoribonucleotides of the invention are believed to signal through a Toll-like receptor (TLR) chosen from TLR9, TLR8, TLR7, and TLR3. Theoligoribonucleotides can also be used in a method to screen for TLRantagonists.
