Oncolytic virus targeting Schistosomes

项目简介：血吸虫病是一种被忽视的热带疾病，影响着数亿人 在全世界范围内，它与严重的发病率和死亡率有关，并造成很高的社会经济负担 对许多受影响的发展中国家。血吸虫病是由水媒寄生吸虫引起的。 血吸虫属，它可以在人类宿主体内存活数十年。疾病病理结果来自 血吸虫卵在宿主组织中的沉积，引起宿主的免疫病理反应。 最近的研究表明，哺乳动物体内宿主范围有限的溶瘤病毒可以消灭癌细胞 不会伤害人类宿主，这些病毒正在积极研究潜在的临床用途。我们 最近进行的初步研究表明，其中一种溶瘤病毒能够感染 血吸虫和寄生虫内的复制。因此，曼氏血吸虫在体外对病毒的暴露 结果100%感染蠕虫，导致被膜破裂，破坏其他蠕虫组织，以及 寄生虫的致命性。与目前用于治疗和控制血吸虫病的药物吡喹酮不同，这种溶瘤药物 病毒影响哺乳动物体内的所有寄生虫期，包括血吸虫幼虫、幼虫和成虫。 这一创新的探索性建议将确认和扩展这些初步研究，目标是 确定感染的动态，以及这种溶瘤病毒是否可以用来感染和潜在地杀死 体内有血吸虫，不会伤害宿主。具体地说，我们将目标1：确定溶瘤的效果 病毒对血吸虫不同生活期的体外作用及目的2：确定溶瘤作用 哺乳动物体内的血吸虫病毒。我们拥有优秀的跨学科合作伙伴 成功实施这一项目。这些目标的实现将成为概念的验证和铺垫。 为了在未来的工作中使用感染和混合感染的动物模型进行更广泛的改进和测试， 了解潜在的寄生虫途径，并针对被病毒劫持的途径，可能导致 新的治疗靶点。这些研究将提供一个潜在地将这种溶瘤病毒用作 由于其宿主范围极窄，可提供一种有效、安全的血吸虫病 有治疗作用。这种方法将很容易转化为治疗和控制的突破性新技术 血吸虫病。

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.