Omega-1 knockdown in Schistosoma mansoni eggs by lentivirus transduction reduces granuloma size in vivo.
Schistosomiasis, one of the most important neglected tropical diseases worldwide, is caused by flatworms (blood flukes or schistosomes) that live in the bloodstream of humans. The hepatointestinal form of this debilitating disease results from a chronic infection with Schistosoma mansoni or Schistosoma japonicum. No vaccine is available to prevent schistosomiasis, and treatment relies predominantly on the use of a single drug, praziquantel. In spite of considerable research effort over the years, very little is known about the complex in vivo events that lead to granuloma formation and other pathological changes during infection. Here we use, for the first time, a lentivirus-based transduction system to deliver microRNA-adapted short hairpin RNAs (shRNAmirs) into the parasite to silence and explore selected protein-encoding genes of S. mansoni implicated in the disease process. This gene-silencing system has potential to be used for functional genomic-phenomic studies of a range of socioeconomically important pathogens.
Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Melbourne, Victoria 3010, Australia.
Jana
J
Hagen
Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Melbourne, Victoria 3010, Australia.
Neil D
ND
Young
Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Melbourne, Victoria 3010, Australia.
Alison L
AL
Every
Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Melbourne, Victoria 3010, Australia.
Charles N
CN
Pagel
Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
Corinna
C
Schnoeller
Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Melbourne, Victoria 3010, Australia.
Jean-Pierre Y
JP
Scheerlinck
Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Melbourne, Victoria 3010, Australia.
Robin B
RB
Gasser
Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Melbourne, Victoria 3010, Australia.
Bernd H
BH
Kalinna
D000818:Animals; D000947:Antigens, Helminth / Q000096:biosynthesis / Q000235:genetics*; D004527:Egg Proteins / Q000096:biosynthesis / Q000235:genetics*; D004531:Eggs / Q000821:virology; D055785:Gene Knockdown Techniques / Q000379:methods*; D020868:Gene Silencing; D006099:Granuloma / Q000469:parasitology* / Q000517:prevention & control; D016086:Lentivirus / Q000235:genetics*; D008807:Mice, Inbred BALB C; D035683:MicroRNAs; D034741:RNA, Small Interfering / Q000235:genetics; D012550:Schistosoma mansoni / Q000821:virology*; D012555:Schistosomiasis mansoni / Q000473:pathology / Q000821:virology*; D014161:Transduction, Genetic / Q000379:methods*
D000947:Antigens, Helminth; D004527:Egg Proteins; D035683:MicroRNAs; D034741:RNA, Small Interfering; C587622:omega-1 antigen, Schistosoma mansoni