Baculovirus induces type I interferon production through toll-like receptor-dependent and -independent pathways in a cell-type-specific manner.
Autographa californica nuclear polyhedrosis virus (AcNPV) is a double-stranded-DNA virus that is pathogenic to insects. AcNPV was shown to induce an innate immune response in mammalian immune cells and to confer protection of mice from lethal viral infection. In this study, we have shown that production of type I interferon (IFN) by AcNPV in murine plasmacytoid dendritic cells (pDCs) and non-pDCs, such as peritoneal macrophages and splenic CD11c+ DCs, was mediated by Toll-like receptor (TLR)-dependent and -independent pathways, respectively. IFN regulatory factor 7 (IRF7) was shown to play a crucial role in the production of type I IFN by AcNPV not only in immune cells in vitro but also in vivo. In mouse embryonic fibroblasts (MEFs), AcNPV produced IFN-beta and IFN-inducible chemokines through TLR-independent and IRF3-dependent pathways, in contrast to the TLR-dependent and IRF3/IRF7-independent production of proinflammatory cytokines. Although production of IFN-beta and IFN-inducible chemokines was severely impaired in IFN promoter-stimulator 1 (IPS-1)-deficient MEFs upon infection with vesicular stomatitis virus, AcNPV produced substantial amounts of the cytokines in IPS-1-deficient MEFs. These results suggest that a novel signaling pathway(s) other than TLR- and IPS-1-dependent pathways participates in the production of type I IFN in response to AcNPV infection.
Abe
Takayuki
T
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
Kaname
Yuuki
Y
Wen
Xiaoyu
X
Tani
Hideki
H
Moriishi
Kohji
K
Uematsu
Satoshi
S
Takeuchi
Osamu
O
Ishii
Ken J
KJ
Kawai
Taro
T
Akira
Shizuo
S
Matsuura
Yoshiharu
Y
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D004266:DNA Virus Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000821:virology; D016899:Interferon-beta / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D017924:Nucleopolyhedroviruses / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D013045:Species Specificity; D051193:Toll-Like Receptors / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D051193:Toll-Like Receptors; D016899:Interferon-beta