Oncolytic virus targeting Schistosomes

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Project summary: Schistosomiasis, a neglected tropical disease affects hundreds of millions of people worldwide and is associated with significant morbidity and mortality and imposes a high socioeconomic burden on many affected developing countries. Schistosomiasis is caused by water-borne parasitic trematodes of the genus Schistosoma, which can survive inside human hosts for decades. Disease pathology results from deposition of schistosome eggs in host tissues, which evokes an immunopathological response from the host. Recent work shows that oncolytic viruses with limited host range in mammals can eliminate cancer cells without harming the human host and these viruses are being actively investigated for potential clinical use. We recently performed preliminary studies showing that one of these oncolytic viruses is capable of infecting schistosomes and replicating within the parasites. Thus, exposure of Schistosoma mansoni to the virus in vitro results in 100% infection of worms, resulting in tegumental disruption, damage to other worm tissues, and parasite lethality. Unlike praziquantel, the current drug used to treat and control schistosomiasis, this oncolytic virus impacts all intramammalian parasite stage including schistosomula, juvenile, and adult schistosomes. This innovative exploratory proposal will confirm and extend these preliminary studies with the goals of determining the dynamics of infection and whether this oncolytic virus can be used to infect and potentially kill schistosomes in vivo without harming the host. Specifically, we will Aim 1: Determine the effects of oncolytic virus on the different life stages of schistosomes in vitro and Aim 2: Determine the effects of oncolytic virus on schistosomes within the mammalian host. We have excellent interdisciplinary collaborators to carry this project successfully. Accomplishment of these aims will serve as proof of concept and set the stage for more extensive refinement and testing in future work using animal models of infection and co-infection to understand the underlying parasite pathways and target the pathway hijacked by the virus, perhaps leading to new therapeutic targets. These studies will provide a platform to potentially use this oncolytic virus as a “schisto-lytic” agent due to its extremely narrow host range and could provide an effective safe schistosomiasis therapeutic. The approach will readily translate into groundbreaking new technology for treatment and control of schistosomiasis.