Abstract
The baculovirus, Autographa californica nuclear polyhedrosis virus (AcNPV), is an insect virus and has been used as a vector for a high level expression of foreign proteins in insect cells. Furthermore, AcNPV has been shown to infect mammalian cells and express foreign genes under the control of the mammalian promoters. We have previously shown that intranasal inoculation of AcNPV induces a strong innate immune response and protects mice from a lethal challenge of influenza viruses. The activation of innate immunity was shown to closely link to the secondary adaptive immune responses of the host. Members of the Toll-like receptor (TLR) family are essential components in this process. The production of inflammatory cytokines was severely reduced in peritoneal macrophages (PEC) and dendritic cells (DC) derived from mice deficient in MyD88 or TLR9 after cultivation with AcNPV. In contrast, a significant amount of interferon (IFN)-α was still detectable in the PEC and DC of the mice after stimulation with AcNPV, suggesting that a TLR9/MyD88-independent signaling pathway might participate in the production of IFN-α by AcNPV. Recently, the cytoplasmic helicase proteins RIG-I and MDA5 have been identified as viral dsRNA detectors to facilitate type-I IFN production through the interaction with an adaptor molecule IPS-1. However, neither RIG-I, MDA5 or IPS-1 was required for the production of type-I IFN and inflammatory cytokine by AcNPV in PEC and DC. These results suggest that novel signaling pathway(s) other than TLR and IPS-1-dependent pathways may participate in the induction of type I IFN in immune competent cells in response to AcNPV infection.
