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

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Author(s)

    • LIU Yuxiu LIU Yuxiu
    • Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo, 4–6–1 Shirokanedai, Minato-ku, Tokyo 108–8639, Japan|College of Veterinary Medicine, Agricultural Division, Jilin University, Changchun 130062, China
    • SATO Hiroki SATO Hiroki
    • Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo, 4–6–1 Shirokanedai, Minato-ku, Tokyo 108–8639, Japan
    • MOONAN Navita Anisia
    • Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo, 4–6–1 Shirokanedai, Minato-ku, Tokyo 108–8639, Japan
    • YONEDA Misako
    • Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo, 4–6–1 Shirokanedai, Minato-ku, Tokyo 108–8639, Japan
    • XIA Xianzhu
    • College of Veterinary Medicine, Agricultural Division, Jilin University, Changchun 130062, China
    • KAI Chieko
    • Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo, 4–6–1 Shirokanedai, Minato-ku, Tokyo 108–8639, Japan

Abstract

Interleukin 18 (IL-18) plays an important role in the T-helper-cell type 1 immune response against intracellular parasites, bacteria and viral infections. It has been widely used as an adjuvant for vaccines and as an anticancer agent. However, IL-18 protein lacks a typical signal sequence and requires cleavage into its mature active form by caspase 1. In this study, we constructed 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. The expressed proIL-18 proteins were processed to their mature forms in the cells. The supernatants of cells transfected with these plasmids induced high interferon-γ production in canine peripheral blood mononuclear cells or mouse splenocytes, respectively, indicating the secretion of bioactive IL-18. Using reverse genetics, we also generated a recombinant canine distemper virus that expresses cIL-18 or mIL-18 fused to the hIL-2 signal sequence. As expected, both recombinant viruses produced mature IL-18 in the infected cells, which secreted bioactive IL-18. These results indicate that the signal sequence from hIL-2 is suitable for the secretion of mature IL-18. These recombinant viruses can also potentially be used as immunoadjuvants and agents for anticancer therapies <i>in vivo</i>.

Journal

  • Journal of Veterinary Medical Science

    Journal of Veterinary Medical Science 76(9), 1241-1248, 2014

    JAPANESE SOCIETY OF VETERINARY SCIENCE

Codes

  • NII Article ID (NAID)
    130004693902
  • NII NACSIS-CAT ID (NCID)
    AA10796138
  • Text Lang
    ENG
  • ISSN
    0916-7250
  • NDL Article ID
    025818512
  • NDL Call No.
    Z18-350
  • Data Source
    NDL  J-STAGE 
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