Suppression of mRNAs encoding CD63 family tetraspanins from the carcinogenic liver fluke Opisthorchis viverrini results in distinct tegument phenotypes

Chaiyadet, Sujittra, Krueajampa, Watchara, Hipkaeo, Wiphawi, Plosan, Yada, Piratae, Supawadee, Sotillo, Javier, Smout, Michael, Sripa, Banchob, Brindley, Paul J., Loukas, Alex, and Laha, Thewarach (2017) Suppression of mRNAs encoding CD63 family tetraspanins from the carcinogenic liver fluke Opisthorchis viverrini results in distinct tegument phenotypes. Scientific Reports, 7. 14342.

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The liver fluke Opisthorchis viverrini infects 10 million people in Southeast Asia and causes cholangiocarcinoma (CCA). Fluke secreted and tegumental proteins contribute to the generation of a tumorigenic environment and are targets for drug and vaccine-based control measures. Herein, we identified two tetraspanins belonging to the CD63 family (Ov-TSP-2 and Ov-TSP-3) that are abundantly expressed in the tegument proteome of O. viverrini. Ov-tsp-2 and tsp-3 transcripts were detected in all developmental stages of O. viverrini. Protein fragments corresponding to the large extracellular loop (LEL) of each TSP were produced in recombinant form and antibodies were raised in rabbits. Ov-TSP-2 and TSP-3 were detected in whole worm extracts and excretory/secretory products of O. viverrini and reacted with sera from infected hamsters and humans. Antibodies confirmed localization of Ov-TSP-2 and TSP-3 to the adult fluke tegument. Using RNA interference, Ov-tsp-2 and tsp-3 mRNA expression was significantly suppressed for up to 21 days in vitro. Ultrastructural observation of tsp-2 and tsp-3 dsRNA-treated flukes resulted in phenotypes with increased tegument thickness, increased vacuolation (tsp-2) and reduced electron density (tsp-3). These studies confirm the importance of CD63 family tegument tetraspanins in parasitic flukes and support efforts to target these proteins for vaccine development.

Item ID: 51614
Item Type: Article (Research - C1)
ISSN: 2045-2322
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Funders: National Health and Medical Research Council of Australia (NHMRC), National Institute of Health (NIH), USA
Projects and Grants: NHMRC 1085309, NIH 5 R01CA164719
Date Deposited: 22 Nov 2017 07:44
FoR Codes: 31 BIOLOGICAL SCIENCES > 3104 Evolutionary biology > 310407 Host-parasite interactions @ 50%
31 BIOLOGICAL SCIENCES > 3101 Biochemistry and cell biology > 310109 Proteomics and intermolecular interactions (excl. medical proteomics) @ 25%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320704 Medical parasitology @ 25%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 50%
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