A proviral role for CpG in cytomegalovirus infection.
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.
Iversen
Ann-Charlotte
AC
Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway. Ann-Charlotte.Iversen@ntnu.no
Steinkjer
Bjørg
B
Nilsen
Nadra
N
Bohnhorst
Janne
J
Moen
Siv Helen
SH
Vik
Randi
R
Stephens
Phil
P
Thomas
David W
DW
Benedict
Chris A
CA
Espevik
Terje
T
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
C513201:CpG-B 2006; D009838:Oligodeoxyribonucleotides; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9