Baculovirus transduction of chondrocytes elicits interferon-α/ β and suppresses transgene expression

Abstract

Background: Baculovirus is an effective vector for gene delivery into primary chondrocytes and repeated baculovirus transduction (i.e. supertransduction) appears to be promising for prolonging transgene expression, but how supertransduction may influence baculovirus-mediated gene delivery is unknown. Methods: We first investigated whether prior baculovirus transduction suppressed the ensuing transgene expression mediated by the supertransduced baculovirus, and then examined whether baculovirus triggered the expression of various cytokines. Whether interferon-α and -β (IFN-α/β) suppressed the transgene expression as well as the pivotal step responsible for the attenuated transgene expression were examined. Results: Baculovirus transduction of chondrocytes elicited an immediate yet transient expression of IFN-α/β, which repressed the transgene expression in a dose-dependent manner. The attenuation was observed for transgene expression driven by different promoters and resulted neither from internalization or nuclear import of baculovirus. Moreover, the attenuation was alleviated if supertransduction was performed when IFN-α/β responses diminished. Baculovirus transduction also triggered the expression of tumor necrosis factor-α and interleukin (IL)-6, but not IL-1β. Despite the induction of these responses, supertransduction of chondrocytes with a baculovirus expressing bone morphogenetic protein-2 successfully enhanced the chondrogenic differentiation and matrix synthesis. Conclusions: Baculovirus transduction of primary chondrocytes elicits antiviral effects that suppress transgene expression. Nonetheless, baculovirus supertransduction comprises a feasible approach to extend transgene expression for cartilage engineering. Copyright © 2009 John Wiley & Sons, Ltd.