title: Characterization of conserved viral leader RNA sequences that stimulate innate immunity through TLRs.
abstract: Viruses of the order Mononegavirales encompass life-threatening pathogens with single-stranded segmented or nonsegmented negative-strand RNA genomes. The RNA genomes are characterized by highly conserved sequences at the extreme untranslated 3' and 5' termini that are most important for virus infection and viral RNA synthetic processes. The 3' terminal genome regions of negative-strand viruses such as vesicular stomatitis virus, Sendai virus, or influenza virus contain a high number of conserved U and G nucleotides, and synthetic oligoribonucleotides encoding such sequences stimulate sequence-dependent cytokine responses via TLR7 and TLR8. Immune cells responding to such sequences include NK cells, NK/T cells, plasmacytoid, and myeloid dendritic cells, as well as monocytes and B cells. Strong Th1 and pro-inflammatory cytokine responses are also induced upon in vivo application of oligoribonucleotides. It appears possible that the presence of highly conserved untranslated terminal regions in the viral genome fulfilling fundamental functions for the viral replication may enable the host to induce directed innate immune defense mechanisms, by allowing pathogen detection through essential RNA regions that the virus cannot readily mutate.
authors: Coley Pharmaceutical GmbH, Düsseldorf, Germany.
authors: Alexandra
authors: A
authors: Forsbach
authors: Jean-Guy
authors: JG
authors: Nemorin
authors: Kirsten
authors: K
authors: Völp
authors: Ulrike
authors: U
authors: Samulowitz
authors: Carmen
authors: C
authors: Montino
authors: Christian
authors: C
authors: Müller
authors: Sibylle
authors: S
authors: Tluk
authors: Svetlana
authors: S
authors: Hamm
authors: Stefan
authors: S
authors: Bauer
authors: Grayson B
authors: GB
authors: Lipford
authors: Jörg
authors: J
authors: Vollmer
mesh_terms: D000818:Animals; D002460:Cell Line; D017124:Conserved Sequence; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D016679:Genome, Viral; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D018096:Mononegavirales / Q000276:immunology* / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000276:immunology* / Q000494:pharmacology; D009843:Oligoribonucleotides / Q000276:immunology* / Q000494:pharmacology; D012367:RNA, Viral / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000276:immunology / Q000378:metabolism*; D051200:Toll-Like Receptor 8 / Q000276:immunology / Q000378:metabolism*
chemical_list: C408982:CPG-oligonucleotide; D016207:Cytokines; D009838:Oligodeoxyribonucleotides; D009843:Oligoribonucleotides; D012367:RNA, Viral; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D007371:Interferon-gamma