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Interaction Between the Neglected Tropical Disease Human Schistosomiasis and HCV Infection in Egypt: a Puzzling Relationship

机译:埃及被忽视的热带病人类血吸虫病与HCV感染之间的相互作用:令人困惑的关系

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摘要

Egypt has the highest prevalence of chronic hepatitis C virus (HCV) infection and seropositivity worldwide, and it has been proposed that this enhanced susceptibility to HCV is related to coinfection with schistosomiasis. Although currently, there are no studies regarding the actual prevalence of both human schistosomiasis and schistosomiasis/HCV coinfection evidences strongly support that eliminating human schistosomiasis from Egypt is necessary to reduce both HCV prevalence and liver pathology. The present review highlights the significant impact of the neglected tropical disease human schistosomiasis on both susceptibility of Egyptians to HCV coinfection, severity of the resulting liver pathology, and poor response to antiviral therapy. The immune evasion mechanisms exerted by the HCV-NS3/4A protease domain, and the possible impact of immune evasion mechanisms exerted by proteases of larval, worm and egg stages of the parasite Schistosoma on human susceptibility to HCV infection are discussed. In addition, schistosome immune evasion mechanisms may include immunosuppression that in turn prevents clearance of HCV viremia and leads to relapsing HCV infection and severe liver pathology. I propose the generation of a replicon system from the most prevailing genotype (HCV-4a) in Egypt and establishing its replication on hepatoplastoma or immune cells in presence of bilharzial antigens. Finally, the use of a humanized small animal model that can acquire both HCV and S. mansoni infections will be important to further understand in real time the impact of coinfection on both the immune system and liver pathology.
机译:埃及是世界上慢性丙型肝炎病毒(HCV)感染和血清阳性率最高的国家,有人提出,这种对HCV的易感性增加与血吸虫病合并感染有关。尽管目前尚无关于人类血吸虫病和血吸虫病/ HCV合并感染的实际患病率的研究,但有力证据表明,从埃及消灭人类血吸虫病对于降低HCV患病率和肝脏病理是必要的。本综述强调了被忽视的热带病人类血吸虫病对埃及人对HCV合并感染的易感性,所导致的肝脏病理的严重性以及对抗病毒治疗的不良反应的重大影响。讨论了HCV-NS3 / 4A蛋白酶结构域发挥的免疫逃逸机制,以及寄生虫血吸虫的幼虫,蠕虫和卵期蛋白酶发挥的免疫逃避机制对人对HCV感染的敏感性。此外,血吸虫的免疫逃逸机制可能包括免疫抑制,从而阻止了HCV病毒血症的清除,并导致HCV感染复发和严重的肝脏病理。我提议从埃及最流行的基因型(HCV-4a)生成复制子系统,并在存在胆管抗原的情况下在肝细胞瘤或免疫细胞上建立复制系统。最后,使用可以同时感染HCV和曼氏沙门氏菌的人源化小动物模型,对于进一步实时了解共感染对免疫系统和肝脏病理的影响非常重要。

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