RNAi-mediated silencing of ARV1 in Setaria digitata impairs in-vitro microfilariae release, embryogenesis and adult parasite viability

• Published in: Veterinary parasitology Vol. 284; p. 109189
• Main Authors: Wickramatunga, Palliya Guruge Thilini Sithara, Gunawardene, Yasanthi Illika Nilmini Silva, Wijesinghe, Kaveesha Jayani, Ellepola, Arjuna N.B., Dassanayake, Ranil Samantha
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2020
• Subjects: Animals; ARV1; Helminth Proteins - genetics; Helminth Proteins - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Microfilariae - genetics; Morphological deformities; RNA Interference; Setaria digitata; Setaria Nematode - embryology; Setaria Nematode - genetics; Setaria Nematode - physiology; ARV1; Morphological deformities; RNA interference; Setaria digitata
• ISSN: 0304-4017; 1873-2550
• DOI: 10.1016/j.vetpar.2020.109189

[Display omitted] •SD-ARV1 expression can be knocked down via siRNA microinjection.•SD-ARV1 knockout worms displayed motility and viability reduction.•siRNA treated adult female worms associated with reduced Mf and egg released.•SD-ARV1 knockdown resulted phenotypic deformities in intrauterine stages and Mf.•SD-ARV1 can be established as a possible, novel anthelmintic drug target. Setaria digitata is a nematode that resides in the peritoneal cavity of ruminants causing cerebrospinal nematodiasis disease affecting livestock and inflicting significant economic forfeitures in Asia. Further, this nematode can infect humans, causing abscesses, allergic reactions, enlarged lymph nodes, eye lesions and inflammation of the lungs. The ‘ARE2 required for viability1’ (ARV1) encodes for putative lipid transporter localized in the endoplasmic reticulum (ER) and Golgi complex membrane in humans and yeast. In the present study, the functional role of S. digitata ARV1 (SD-ARV1) was investigated using RNA interference (RNAi) reverse genetic tool. The targeted silencing SD-ARV1 transcripts by siRNA mediated RNAi resulted in a dramatic reduction of SD-ARV1 gene and protein expressions in S. digitata, which in turn modulated the parasitic motility, its production of eggs and microfilaria viability. Further, the same silencing caused severe phenotypic deformities such as distortion of eggs and embryonic development arrest in the intrauterine stages of adult female S. digitata. These results suggest that SD-ARV1 plays a pivotal role in worm embryogenesis, adult parasite motility and microfilariae viability. Finally, the ubiquitous presence of ARV1 in human filarial nematodes, its crucial functional roles in nematode biology and its remarkable diversity in primary protein structure compared to homologues in their hosts warrants further investigations to ascertain its candidacy in anthelmintic drug development.