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Vector-based RNA interference of cathepsin B1 in Schistosoma mansoni

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Abstract

In helminth parasites, proteolytic enzymes have been implicated in facilitating host invasion, moulting, feeding, and evasion of the host immune response. These key functions render them potential targets for anti-parasite chemotherapy and immunotherapy. Schistosomes feed on host blood and the digested haemoglobin is their major source of amino acids. Haemoglobin digestion is essential for parasite development, growth, and reproduction. We recently reported the use of pseudotyped Moloney murine leukaemia virus to accomplish transformation of Schistosoma mansoni. Here, we report the design of a viral vector expressing a dsRNA hairpin to silence expression of the schistosome cathepsin B1 (SmCB1) gene. We observed 80% reduction in transcript level 72 h after virus exposure and complete silencing of enzyme activity in transduced worms. This is the first report using this technology in any helminth parasite. It will facilitate the evaluation of potential drug targets and biochemical pathways for novel interventions in schistosomes.

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Acknowledgments

Schistosome-infected snails were provided by Dr. Fred A. Lewis, Biomedical Research Institute, Rockville, MD, USA, National Institute of Allergy and Infectious Disease (NIAID) Contract N01-A1-30026. We gratefully acknowledge the expert advice from Ms. Mary Duke (QMIR, Brisbane, Australia) regarding the establishment of the schistosome life cycle and Mrs. Jane Howard (University of Melbourne, Australia) for technical expertise in producing the virus. The research was supported by NIH-NIAID award number RO1AI072773 to PJB and BHK and by a project grant of the Australian National Health and Medical Research Council (App ID 454422) to BHK and PJB.

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Authors and Affiliations

  1. Centre for Animal Biotechnology, Faculty of Veterinary Science, The University of Melbourne, Parkville, VIC, 3052, Australia

    Elissaveta B. Tchoubrieva & Bernd H. Kalinna

  2. Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, 3800, Australia

    Poh C. Ong & Robert N. Pike

  3. Department of Microbiology, Immunology and Tropical Medicine, George Washington University Medical Centre, Washington, DC, 20037, USA

    Paul J. Brindley

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  1. Elissaveta B. Tchoubrieva
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  2. Poh C. Ong
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  5. Bernd H. Kalinna
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Correspondence to Bernd H. Kalinna.

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Tchoubrieva, E.B., Ong, P.C., Pike, R.N. et al. Vector-based RNA interference of cathepsin B1 in Schistosoma mansoni . Cell. Mol. Life Sci. 67, 3739–3748 (2010). https://doi.org/10.1007/s00018-010-0345-3

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