Abstract
Based on its ability to express high levels of protein, baculovirus has been widely used for recombinant protein production in insect cells for more than thirty years with continued technical improvements. In addition, baculovirus has been successfully applied for foreign gene delivery into mammalian cells without any viral replication. However, several CpG motifs are present throughout baculoviral DNA and induce an antiviral response in mammalian cells, resulting in the production of pro-inflammatory cytokines and type I interferon through a Toll-like receptor (TLR)-dependent or -independent signaling pathway, and ultimately limiting the efficiency of transgene expression. On the other hand, by taking advantage of this strong adjuvant activity, recombinant baculoviruses encoding neutralization epitopes can elicit protective immunity in mice. Moreover, immunodeficient cells, such as hepatitis C virus (HCV)- or human immunodeficiency virus (HIV)-infected cells, are more susceptible to baculovirus infection than normal cells and are selectively eliminated by the apoptosis-inducible recombinant baculovirus. Here, we summarize the application of baculovirus as a gene expression vector and the mechanism of the host innate immune response induced by baculovirus in mammalian cells. We also discuss the future prospects of baculovirus vectors.
Highlights
Baculovirus has been widely used as a gene expression tool for more than thirty years based on its ability to express high levels of proteins in insect cells
Along with the progress of baculovirus research, recombinant baculoviruses have been shown to be capable of entering into various mammalian cells and of expressing foreign genes under the control of mammalian promoters without any viral replication [1,2,3,4,5,6]; as a result, they have been applied for gene delivery into mammalian cells
In a study using knockout mice, we revealed that a TLR9/MyD88-dependent recognition pathway participates in the production of type I IFNs, inflammatory cytokines and IFNDNA recognition pathway participates in the production of type I IFNs, inflammatory cytokines and inducible chemokines and the activation of NF-κB in mouse immune cells such as macrophages or IFN-inducible chemokines and the activation of NF-κB in mouse immune cells such as macrophages or dendritic cells (DCs) in response to the Autographa californica multiple NPV (AcMNPV) genome [9,10]
Summary
Baculovirus has been widely used as a gene expression tool for more than thirty years based on its ability to express high levels of proteins in insect cells. Along with the progress of baculovirus research, recombinant baculoviruses have been shown to be capable of entering into various mammalian cells and of expressing foreign genes under the control of mammalian promoters without any viral replication [1,2,3,4,5,6]; as a result, they have been applied for gene delivery into mammalian cells. The advantages of the baculovirus gene expression system are its high transgene capacity; its enabling of both easy construction of recombinant virus with a bacmid system [7] and posttranslational modification with a eukaryotic system such as glycosylation; and, especially in mammalian cells, its replication-defect property—namely, the absence of primary antibody and low cytotoxicity compared to mammalian virus-derived vectors. We describe the properties of baculovirus as a tool for gene delivery, gene therapy and vaccine development
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