Abstract
Baculovirus expression systems have been widely used to produce recombinant mammalian proteins owing to the lack of viral replication in vertebrates. Although several lines of evidence have demonstrated impacts of baculovirus infection in mammalian hosts, genome-wide effects have not been fully elucidated. Here, we provide comparative transcriptome profiles of baculovirus and host-immune response genes in recombinant baculovirus-infected mammalian and insect cells. Specifically, to decipher the impacts of baculovirus infection in mammalian cells, we conducted total RNA-seq on human 293TT cells and insect Sf9 cells infected with recombinant baculovirus. We found that baculovirus genes were rarely expressed under the control of baculoviral promoters in 293TT cells. Although some baculovirus early genes, such as PE38 and IE-01, showed limited expression in 293TT cells, baculoviral late genes were mostly silent. We also found modest induction of a small number of mammalian immune response genes associated with Toll-like receptors, cytokine signaling, and complement in baculovirus-infected 293TT cells. These comprehensive transcriptome data will contribute to improving recombinant baculovirus as tools for gene delivery, gene therapy, and vaccine development.
Highlights
IntroductionBaculoviruses primarily use insects as a host to produce viral progenies, they are capable of infecting some mammalian cells, despite deficiencies in their ability to replicate in these cells [1]
Baculoviruses have been extensively used for decades as eukaryotic gene expression systems. baculoviruses primarily use insects as a host to produce viral progenies, they are capable of infecting some mammalian cells, despite deficiencies in their ability to replicate in these cells [1]
Baculoviruses primarily use insects as a host to produce viral progenies, they are capable of infecting some mammalian cells, despite deficiencies in their ability to replicate in these cells [1]
Summary
Baculoviruses primarily use insects as a host to produce viral progenies, they are capable of infecting some mammalian cells, despite deficiencies in their ability to replicate in these cells [1]. This unique feature allows baculoviruses to serve as potent and safe mammalian gene-delivery systems [2,3]. Baculovirus expression systems offer some additional benefits compared with other currently used gene expression systems. Unlike bacterial expression systems, baculovirus systems support post-translational modifications, enabling production of mammalian proteins in their native form [4]. Compared with adeno-associated virus (AAV) vectors, which have a limited gene insertion capacity (~4.7 kb), baculoviruses can accept large (>100 kbp) foreign DNA fragments [2]
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