Construction of an Expression System for Bioactive IL-18 and Generation ofRecombinant Canine Distemper Virus Expressing IL-18

[摘要] References(40)Cited-By(1)Interleukin 18 (IL-18) playsan important role in the T-helper-cell type 1 immune response against intracellularparasites, bacteria and viral infections. It has been widely used as an adjuvant forvaccines and as an anticancer agent. However, IL-18 protein lacks a typical signalsequence and requires cleavage into its mature active form by caspase 1. In this study, weconstructed mammalian expression vectors carrying cDNA encoding mature canine IL-18(cIL-18) or mouse IL-18 (mIL-18) fused to the human IL-2 (hIL-2) signal sequence. Theexpressed proIL-18 proteins were processed to their mature forms in the cells. Thesupernatants of cells transfected with these plasmids induced high interferon-γ productionin canine peripheral blood mononuclear cells or mouse splenocytes, respectively,indicating the secretion of bioactive IL-18. Using reverse genetics, we also generated arecombinant canine distemper virus that expresses cIL-18 or mIL-18 fused to the hIL-2signal sequence. As expected, both recombinant viruses produced mature IL-18 in theinfected cells, which secreted bioactive IL-18. These results indicate that the signalsequence from hIL-2 is suitable for the secretion of mature IL-18. These recombinantviruses can also potentially be used as immunoadjuvants and agents for anticancertherapies in vivo.

[学科分类] 兽医学

[关键词] canine distemper virus;interferon-γ;interleukin 18