柯萨奇病毒B1(CVB1),具有多种临床表现的肠道病毒,与潜在的长期后果有关,包括手,脚,和口蹄疫(HFMD),在一些病人。然而,相关的动物模型,传输动力学,CVB1的长期组织嗜性尚未得到系统表征。在这项研究中,我们建立了恒河猴CVB1呼吸道感染模型,并评估了临床症状,病毒载量,急性期(0-14天)和长期恢复期(15-30天)的免疫水平。我们还调查了分布情况,病毒清除,使用感染后30天(d.p.i.)收集的35个死后恒河猴组织样本,以及长期恢复期的病理学。结果表明,感染的恒河猴对CVB1易感,并表现出手足口病症状,病毒清除,细胞因子水平改变,以及中和抗体的存在。尸检显示心脏病毒载量呈阳性,脾,脾胰腺,软腭,和嗅球组织。HE染色显示肝脏病理损伤,脾,脾肺,软腭,和气管上皮.在d.p.i.30,在内脏中检测到病毒抗原,免疫,呼吸,和肌肉组织,但不在肠或神经组织中。脑组织检查显示病毒性脑膜炎样改变,并在枕骨中检测到CVB1抗原表达,脑桥,小脑,和30d.p.i.的脊髓组织。这项研究为HFMD的非人灵长类动物模型中CVB1的发病机理提供了第一个见解,并证实了CVB1在长期感染后表现出组织嗜性。
Coxsackievirus B1 (CVB1), an enterovirus with multiple clinical presentations, has been associated with potential long-term consequences, including hand, foot, and mouth disease (HFMD), in some patients. However, the related animal models, transmission dynamics, and long-term tissue tropism of CVB1 have not been systematically characterized. In this study, we established a model of CVB1 respiratory infection in rhesus macaques and evaluated the clinical symptoms, viral load, and immune levels during the acute phase (0-14 days) and long-term recovery phase (15-30 days). We also investigated the distribution, viral clearance, and pathology during the long-term recovery period using 35 postmortem rhesus macaque tissue samples collected at 30 days postinfection (d.p.i.). The results showed that the infected rhesus macaques were susceptible to CVB1 and exhibited HFMD symptoms, viral clearance, altered cytokine levels, and the presence of neutralizing antibodies. Autopsy revealed positive viral loads in the heart, spleen, pancreas, soft palate, and olfactory bulb tissues. HE staining demonstrated pathological damage to the liver, spleen, lung, soft palate, and tracheal epithelium. At 30 d.p.i., viral antigens were detected in visceral, immune, respiratory, and muscle tissues but not in intestinal or neural tissues. Brain tissue examination revealed viral meningitis-like changes, and CVB1 antigen expression was detected in occipital, pontine, cerebellar, and spinal cord tissues at 30 d.p.i. This study provides the first insights into CVB1 pathogenesis in a nonhuman primate model of HFMD and confirms that CVB1 exhibits tissue tropism following long-term infection.