Do microbiomes of parasitic nematodes contribute to disease pathogenesis?

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• Professor Mark Taylor, Liverpool School of Tropical Medicine
• Wednesday 05 March 2025, 13:00-14:00
• Seminar Room, Tennis Court Road, Dept of Pathology..

If you have a question about this talk, please contact Maria Duque-Correa, mad75.

Recently we have discovered that 70% of parasitic nematodes host a large and diverse RNA virome (Quek et al. 2024, Nature Microbiology). Previous work in our laboratory has highlighted the contribution of Wolbachia bacterial endosymbionts as drivers of inflammatory disease pathogenesis. Does the newly discovered RNA virome also contribute to disease pathogenesis? We have focussed on a rhabdovirus, OVRV1 , which is ubiquitous in endemic onchocerciasis populations and elicits antibody responses in infected or exposed communities. OVRV1 is phylogenetically related to lyssaviruses, including rabies, and as such may contribute to the disease pathogenesis of onchocerciasis associated epilepsy. To determine the fusogenicity and the resulting tropism of OVRV1 glycoprotein (gp) we have created lentiviral pseudotypes decorated with OVRV1 glycoproteins to define human cell susceptibility to infection. Pseudotyped lentiviruses provide an opportunity for rapid throughput to determine the functionality of putative viral glycoproteins, as well as provide mechanistic and tropism information in the absence of isolated infectious virus. To probe for cell susceptibility to OVRV1 gp-mediated entry, we exposed human cell lines of different origins (IRF3 KO lung epithelial A549 cells, embryonic kidney HEK293T cells and TZM -bl cells, a derivate of human cervix carcinoma HeLa cells) to GFP -encoding lentiviral particles decorated with OVRV1 -gp. Subsequently, we quantified reporter expression two days post-transduction, with vesicular stomatitis virus (VSV)-gp pseudotypes used as positive control and rhabdoviral reference. Addition of OVRV1 -gp lentiviral pseudotypes to cells generated GFP expression in a dose-dependent manner, providing robust evidence for the ability of OVRV1 gp to mediate entry into human cells and strengthening our hypothesis of OVRV1 infection-induced pathogenesis in humans. Current experiments are testing the susceptibility of advanced human induced pluripotent stem cells (iPSC)-derived bi/tri-partite neurospheroid culture systems to determine OVRV1 infection of neural cells and tissues.

This talk is part of the Parasitology Seminars series.

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