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SUMMARY:Do microbiomes of parasitic nematodes contribute to disease pathog
 enesis? - Professor Mark Taylor\, Liverpool School of Tropical Medicine
DTSTART:20250305T130000Z
DTEND:20250305T140000Z
UID:TALK226987@talks.cam.ac.uk
CONTACT:128182
DESCRIPTION:Recently we have discovered that 70% of parasitic nematodes ho
 st a large and diverse RNA virome (Quek et al. 2024\, Nature Microbiology)
 . Previous work in our laboratory has highlighted the contribution of _Wol
 bachia_ bacterial endosymbionts as drivers of inflammatory disease pathoge
 nesis. Does the newly discovered RNA virome also contribute to disease pat
 hogenesis? We have focussed on a rhabdovirus\, OVRV1\, which is ubiquitous
  in endemic onchocerciasis populations and elicits antibody responses in i
 nfected or exposed communities. OVRV1 is phylogenetically related to lyssa
 viruses\, including rabies\, and as such may contribute to the disease pat
 hogenesis of onchocerciasis associated epilepsy. To determine the fusogeni
 city 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 oppo
 rtunity for rapid throughput to determine the functionality of putative vi
 ral glycoproteins\, as well as provide mechanistic and tropism information
  in the absence of isolated infectious virus. To probe for cell susceptibi
 lity to OVRV1 gp-mediated entry\, we exposed human cell lines of different
  origins (IRF3 KO lung epithelial A549 cells\, embryonic kidney HEK293T ce
 lls 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 vesic
 ular stomatitis virus (VSV)-gp pseudotypes used as positive control and rh
 abdoviral reference. Addition of OVRV1-gp lentiviral pseudotypes to cells 
 generated GFP expression in a dose-dependent manner\, providing robust evi
 dence for the ability of OVRV1 gp to mediate entry into human cells and st
 rengthening our hypothesis of OVRV1 infection-induced pathogenesis in huma
 ns. Current experiments are testing the susceptibility of advanced human i
 nduced pluripotent stem cells (iPSC)-derived bi/tri-partite neurospheroid 
 culture systems to determine OVRV1 infection of neural cells and tissues.
LOCATION:Seminar Room\, Tennis Court Road\, Dept of Pathology.
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