title: Torquetenovirus DNA drives proinflammatory cytokines production and secretion by immune cells via toll-like receptor 9.
abstract: Active infection with torquetenovirus (TTV) has been associated with an increased severity of diseases in which inflammation plays a particularly important pathogenetic role. Here, we report that cloned DNA of a genogroup 4 TTV (ViPiSAL) is an activator of proinflammatory cytokine production by murine spleen cells and that the effect is mediated via toll-like receptor (TLR)9. The same DNA also increased the levels of proinflammatory cytokines induced by two well-characterized TLR9 stimulants. Finally, in silico analyses of the genomes of ViPiSAL and other TTVs revealed marked differences in the representation of CpG motifs known to be most effective at activating immune cells via TLR9. These findings demonstrate for the first time that at least one TTV isolate has the potential to stimulate and co-stimulate inflammatory responses.
authors.affiliation: Virology Unit and Retrovirus Centre, Pisa University Hospital and Department of Experimental Pathology, University of Pisa, 56127 Pisa, Italy.
authors.forename: Jara
authors.initials: J
authors.lastname: Rocchi
authors.forename: Valentina
authors.initials: V
authors.lastname: Ricci
authors.forename: Melania
authors.initials: M
authors.lastname: Albani
authors.forename: Letizia
authors.initials: L
authors.lastname: Lanini
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Andreoli
authors.forename: Lisa
authors.initials: L
authors.lastname: Macera
authors.forename: Mauro
authors.initials: M
authors.lastname: Pistello
authors.forename: Luca
authors.initials: L
authors.lastname: Ceccherini-Nelli
authors.forename: Mauro
authors.initials: M
authors.lastname: Bendinelli
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Maggi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018899:CpG Islands; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression; D016679:Genome, Viral; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000821:virology; D051217:Toll-Like Receptor 9 / Q000378:metabolism*; D022783:Torque teno virus / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D016207:Cytokines; D004279:DNA, Viral; D018836:Inflammation Mediators; D015850:Interleukin-6; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D016753:Interleukin-10; D007371:Interferon-gamma