Based on its ability to express high levels of protein, baculovirus has been widely used for\nrecombinant protein production in insect cells for more than thirty years with continued technical\nimprovements. In addition, baculovirus has been successfully applied for foreign gene delivery into\nmammalian cells without any viral replication. However, several CpG motifs are present throughout\nbaculoviral DNA and induce an antiviral response in mammalian cells, resulting in the production\nof pro-inflammatory cytokines and type I interferon through a Toll-like receptor (TLR)-dependent\nor -independent signaling pathway, and ultimately limiting the efficiency of transgene expression.\nOn the other hand, by taking advantage of this strong adjuvant activity, recombinant baculoviruses\nencoding neutralization epitopes can elicit protective immunity in mice. Moreover, immunodeficient\ncells, such as hepatitis C virus (HCV)- or human immunodeficiency virus (HIV)-infected cells,\nare more susceptible to baculovirus infection than normal cells and are selectively eliminated by the\napoptosis-inducible recombinant baculovirus. Here, we summarize the application of baculovirus\nas a gene expression vector and the mechanism of the host innate immune response induced by\nbaculovirus in mammalian cells. We also discuss the future prospects of baculovirus vectors.
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