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Suppression of mRNAs encoding CD63 family tetraspanins from the carcinogenic liver fluke Opisthorchis viverrini results in distinct tegument phenotypes.
- Source :
-
Scientific reports [Sci Rep] 2017 Oct 30; Vol. 7 (1), pp. 14342. Date of Electronic Publication: 2017 Oct 30. - Publication Year :
- 2017
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Abstract
- 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.
- Subjects :
- Amino Acid Sequence
Animals
Bile Duct Neoplasms pathology
Bile Ducts, Intrahepatic metabolism
Carcinogenesis genetics
Cholangiocarcinoma genetics
Cholangiocarcinoma pathology
Humans
Liver metabolism
Liver parasitology
Mesocricetus
Opisthorchis parasitology
Phenotype
Phylogeny
Proteome metabolism
RNA Interference
RNA, Double-Stranded
RNA, Messenger genetics
RNA, Messenger physiology
Rabbits
Tetraspanin 30 genetics
Tetraspanins genetics
Trematoda parasitology
Cholangiocarcinoma metabolism
Tetraspanin 30 metabolism
Tetraspanins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 29084967
- Full Text :
- https://doi.org/10.1038/s41598-017-13527-5