Pediatric Research Institute, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), China International Science and Technology Cooperation base of Child development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, PR China; Chongqing Shapingba District People's Hospital, Shapingba District, Chongqing, 400014, China.
Pediatric Research Institute, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), China International Science and Technology Cooperation base of Child development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, PR China.
Microb Pathog. 2019 Dec;137:103749. doi: 10.1016/j.micpath.2019.103749. Epub 2019 Sep 12.
Human respiratory syncytial virus (RSV) is the most common viral pathogen of lower respiratory tract infection worldwide. The virus selectively infects the respiratory epithelium, and causes diseases of variable severity in infants and the elderly. However, the differences in pathogenesis in the age groups remain poorly studied. Age is a major determinant of RSV disease, and the most severe morbidity and mortality occur in the infants and the elderly, because of the immature immunity in infants and declining immunity in old age. The cotton rat is a good model of RSV infection as it is naturally susceptible to RSV. In this study, we established an infant/adult/elderly RSV infection model in 3-week, 8-week and 30-week-old cotton rats and infected them with equal dose of RSV. This model exhibited airway neutrophils infiltration. In the 3-week-old group, higher viral load was observed in the lungs and noses, may due to low IFN-α/Mx2 levels. In contrast, the 8-week-old group had adequate IFN-α/Mx2 but exhibited the most obvious pulmonary inflammation and peribronchiolitis. Interestingly, the most severe pathology and delayed viral clearance in the lungs were observed in the 30-week-old group, may related to the increase of mucus induced by TNF-α and the lower antiviral effect of IFN-α. These results clearly revealed that an age-dependent severity of RSV disease and antiviral defense in the cotton rats, which may provide an effective model for personalized vaccine research and specific treatment strategies for different RSV age groups.
人类呼吸道合胞病毒（RSV）是全球下呼吸道感染最常见的病毒病原体。该病毒选择性感染呼吸道上皮细胞，在婴儿和老年人中引起严重程度不同的疾病。然而，年龄组之间的发病机制差异仍研究不足。年龄是 RSV 疾病的主要决定因素，最严重的发病率和死亡率发生在婴儿和老年人中，因为婴儿的免疫力不成熟，老年人的免疫力下降。棉鼠是 RSV 感染的良好模型，因为它天然易感染 RSV。在这项研究中，我们建立了 3 周、8 周和 30 周龄棉鼠的婴儿/成人/老年 RSV 感染模型，并以等量 RSV 感染它们。该模型表现出气道中性粒细胞浸润。在 3 周龄组中，肺部和鼻腔中的病毒载量更高，可能是由于 IFN-α/Mx2 水平较低。相比之下，8 周龄组具有足够的 IFN-α/Mx2，但表现出最明显的肺部炎症和细支气管炎。有趣的是，在 30 周龄组中观察到最严重的肺部病理和病毒清除延迟，可能与 TNF-α 诱导的粘液增加和 IFN-α 的抗病毒作用降低有关。这些结果清楚地表明，棉鼠的 RSV 疾病和抗病毒防御存在年龄依赖性，这可能为不同 RSV 年龄组的个性化疫苗研究和特定治疗策略提供有效模型。
