title: Innate immune response induced by baculovirus attenuates transgene expression in mammalian cells.
abstract: The baculovirus Autographa californica nucleopolyhedrovirus (AcNPV) has been widely used to achieve a high level of foreign gene expression in insect cells, as well as for efficient gene transduction into mammalian cells without any replication. In addition to permitting efficient gene delivery, baculovirus has been shown to induce host innate immune responses in various mammalian cells and in mice. In this study, we examined the effects of the innate immune responses on gene expression by recombinant baculoviruses in cultured cells. The reporter gene expression in IRF3-deficient mouse embryonic fibroblasts (MEFs) infected with the recombinant baculovirus was shown to be enhanced in accordance with the suppression of beta interferon (IFN-β) production. Furthermore, efficient gene transduction by the recombinant baculovirus was achieved in MEFs deficient for stimulator of interferon genes (STING), TANK binding kinase 1 (TBK1), IFN regulatory factor 3 (IRF3), or IFN-β promoter stimulator 1 (IPS-1), but not in those deficient for IRF7, MyD88, or Z-DNA binding protein 1 (ZBP1)/DAI. Enhancement of gene expression by the recombinant baculovirus was also observed in human hepatoma cell lines replicating hepatitis C virus (HCV), in which innate immunity was impaired by the cleavage of IPS-1 by the viral protease. In addition, infection with the recombinant baculovirus expressing the BH3-only protein, BIMS, a potent inducer of apoptosis, resulted in a selective cell death in the HCV replicon cells. These results indicate that innate immune responses induced by infection with baculovirus attenuate transgene expression, and this characteristic might be useful for a selective gene transduction into cells with impaired innate immunity arising from infection with various viruses.
authors: Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors: Chikako
authors: C
authors: Ono
authors: Akinori
authors: A
authors: Ninomiya
authors: Satomi
authors: S
authors: Yamamoto
authors: Takayuki
authors: T
authors: Abe
authors: Xiauyu
authors: X
authors: Wen
authors: Takasuke
authors: T
authors: Fukuhara
authors: Miwa
authors: M
authors: Sasai
authors: Masahiro
authors: M
authors: Yamamoto
authors: Tatsuya
authors: T
authors: Saitoh
authors: Takashi
authors: T
authors: Satoh
authors: Taro
authors: T
authors: Kawai
authors: Ken J
authors: KJ
authors: Ishii
authors: Shizuo
authors: S
authors: Akira
authors: Toru
authors: T
authors: Okamoto
authors: Yoshiharu
authors: Y
authors: Matsuura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D015151:Immunoblotting; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009036:Moths / Q000821:virology; D017924:Nucleopolyhedroviruses / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D014161:Transduction, Genetic; D019076:Transgenes / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; C505371:MAVS protein, human