未经证实:HEV变种,例如Paslahepevirus种balayani(HEV-A)和大鼠HEV(Rocahepevirusratti;HEV-C1)中的猪基因型,可在免疫功能低下的个体中引起慢性戊型肝炎。很少有可靠和容易获得的小动物模型能够准确反映慢性HEV感染。我们旨在开发一种免疫受损的慢性戊型肝炎感染大鼠模型。
未经证实:在这项动物模型感染研究中,用药物组合(泼尼松龙,他克莫司,和霉酚酸酯)通常由移植接受者服用。用源自人和大鼠的HEV-C1菌株或源自人的HEV-A菌株攻击大鼠。病毒载量,肝功能,肝脏组织学,幽默,监测细胞免疫反应。
UNASSIGNED:与低剂量(LD)免疫抑制剂治疗和免疫活性(IC)大鼠的短暂感染相比,高剂量(HD)免疫抑制方案可持续延长大鼠的人和大鼠来源的HEV-C1感染(感染后长达12周)。粪便中平均HEV-C1病毒载量,血清,HD方案治疗的大鼠的肝组织高于LD或IC大鼠(p<0.05)。在慢性感染的大鼠中观察到丙氨酸转氨酶升高,这与肝组织中的组织学肝炎和HEV-C1抗原表达一致。无(0/6)的HD方案治疗,5/6LD方案治疗,和6/6IC大鼠在物种特异性免疫印迹中产生了针对HEV-C1的抗体。在HD方案治疗的大鼠中,免疫抑制的逆转与病毒血症的清除和HEV-C1特异性体液和细胞免疫反应的恢复有关。在接受治疗的慢性戊型肝炎患者中,通过i.p.利巴韦林治疗观察到病毒载量抑制的模拟模式。HD方案治疗的大鼠仍然不易感染HEV-A。
UNASSIGNED:我们开发了一种可扩展的慢性戊型肝炎免疫抑制大鼠模型,该模型与移植受者的这种感染表型非常相似。
UNASSIGNED:人类慢性戊型肝炎的研究需要方便的小动物模型。我们通过用人类常用的药物作为器官移植排斥预防来抑制大鼠的免疫反应,开发了慢性戊型肝炎的动物模型。该模型紧密地模仿了人类慢性戊型肝炎的特征。
UNASSIGNED: HEV variants such as swine genotypes within Paslahepevirus species balayani (HEV-A) and rat HEV (Rocahepevirus ratti; HEV-C1) cause chronic hepatitis E in immunocompromised individuals. There are few reliable and accessible small animal models that accurately reflect chronic HEV infection. We aimed to develop an immunocompromised rat model of chronic hepatitis E infection.
UNASSIGNED: In this animal model infection study, rats were immunosuppressed with a drug combination (prednisolone, tacrolimus, and mycophenolate mofetil) commonly taken by transplant recipients. Rats were challenged with human- and rat-derived HEV-C1 strains or a human-derived HEV-A strain. Viral load, liver function, liver histology, humoural, and cellular immune responses were monitored.
UNASSIGNED: A high-dose (HD) immunosuppressive regimen consistently prolonged human- and rat-derived HEV-C1 infection in rats (up to 12 weeks post infection) compared with transient infections in low-dose (LD) immunosuppressant-treated and immunocompetent (IC) rats. Mean HEV-C1 viral loads in stool, serum, and liver tissue were higher in HD regimen-treated rats than in LD or IC rats (p <0.05). Alanine aminotransferase elevation was observed in chronically infected rats, which was consistent with histological hepatitis and HEV-C1 antigen expression in liver tissue. None (0/6) of the HD regimen-treated, 5/6 LD regimen-treated, and 6/6 IC rats developed antibodies to HEV-C1 in species-specific immunoblots. Reversal of immunosuppression was associated with clearance of viraemia and restoration of HEV-C1-specific humoural and cellular immune responses in HD regimen-treated rats, mimicking patterns in treated patients with chronic hepatitis E. Viral load suppression was observed with i.p. ribavirin treatment. HD regimen-treated rats remained unsusceptible to HEV-A infection.
UNASSIGNED: We developed a scalable immunosuppressed rat model of chronic hepatitis E that closely mimics this infection phenotype in transplant recipients.
UNASSIGNED: Convenient small animal models are required for the study of chronic hepatitis E in humans. We developed an animal model of chronic hepatitis E by suppressing immune responses of rats with drugs commonly taken by humans as organ transplant rejection prophylaxis. This model closely mimicked features of chronic hepatitis E in humans.