title: A proviral role for CpG in cytomegalovirus infection.
abstract: TLR9-dependent signaling in plasmacytoid dendritic cells is a key contributor to innate immune defense to mouse CMV infection. We aimed to study the expression and potential contribution of TLR9 signaling in human CMV (HCMV) infection of primary fibroblasts. HCMV infection strongly induced TLR9 expression in two of three fibroblast types tested. Furthermore, the TLR9 ligand CpG-B induced a strong proviral effect when added shortly after HCMV infection, enhancing virus production and cell viability. However, not all CpG classes displayed proviral activity, and this correlated with their IFN-beta-inducing ability. The proviral effect of CpG-B correlated completely with concurrent viral up-regulation of TLR9 in fibroblasts. Importantly, the timing of CpG addition was a critical parameter; in striking contrast to the proviral effect, CpG addition at the time of infection blocked viral uptake and nearly abolished HCMV production. The contrasting and time-dependent effects of CpG on HCMV infectivity reveal a complex interplay between CpG, TLR9, and HCMV infection. Additionally, the data suggest a potentially harmful role for CpG in the promotion of HCMV infection.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway. Ann-Charlotte.Iversen@ntnu.no
authors.forename: Ann-Charlotte
authors.initials: AC
authors.lastname: Iversen
authors.forename: Bjørg
authors.initials: B
authors.lastname: Steinkjer
authors.forename: Nadra
authors.initials: N
authors.lastname: Nilsen
authors.forename: Janne
authors.initials: J
authors.lastname: Bohnhorst
authors.forename: Siv Helen
authors.initials: SH
authors.lastname: Moen
authors.forename: Randi
authors.initials: R
authors.lastname: Vik
authors.forename: Phil
authors.initials: P
authors.lastname: Stephens
authors.forename: David W
authors.initials: DW
authors.lastname: Thomas
authors.forename: Chris A
authors.initials: CA
authors.lastname: Benedict
authors.forename: Terje
authors.initials: T
authors.lastname: Espevik
mesh_terms: D000328:Adult; D002460:Cell Line; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology*; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000821:virology; D006801:Humans; D007231:Infant, Newborn; D009838:Oligodeoxyribonucleotides / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D011533:Proviruses / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
chemical_list: C513201:CpG-B 2006; D009838:Oligodeoxyribonucleotides; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9