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哺乳动物呼肠孤病毒感染小鼠会导致全身性感染,并伴有年龄和病毒株依赖性肺炎和脑炎。

Respiratory infection of mice with mammalian reoviruses causes systemic infection with age and strain dependent pneumonia and encephalitis.

机构信息

Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, Ontario K1H 8M5, Canada.

出版信息

Virol J. 2013 Mar 1;10:67. doi: 10.1186/1743-422X-10-67.

Abstract

BACKGROUND

Because mammalian reoviruses are isolated from the respiratory tract we modeled the natural history of respiratory infection of adult and suckling mice with T1 Lang (T1L) and T3 Dearing (T3D) reoviruses.

METHODS

Adult and suckling Balb/c mice were infected by the intranasal route and were assessed for dose response of disease as well as viral replication in the lung and other organs. Viral antigen was assessed by immunofluorescence and HRP staining of tissue sections and histopathology was assessed on formalin fixed, H + E stained tissue sections.

RESULTS

Intranasal infection of adult mice resulted in fatal respiratory distress for high doses (10(7) pfu) of T1L but not T3D. In contrast both T1L and T3D killed suckling mice at moderate viral dosages (10(5) pfu) but differed in clinical symptoms where T1L induced respiratory failure and T3D caused encephalitis. Infections caused transient viremia that resulted in spread to peripheral tissues where disease correlated with virus replication, and pathology. Immunofluorescent staining of viral antigens in the lung showed reovirus infection was primarily associated with alveoli with lesser involvement of bronchiolar epithelium. Immunofluorescent and HRP staining of viral antigens in brain showed infection of neurons by T3D and glial cells by T1L.

CONCLUSIONS

These mouse models of reovirus respiratory infection demonstrated age and strain dependent disease that are expected to be relevant to understanding and modulating natural and therapeutic reovirus infections in humans.

摘要

背景

由于哺乳动物呼肠孤病毒是从呼吸道中分离出来的,我们用 T1 Lang(T1L)和 T3 Dearing(T3D)呼肠孤病毒对成年和哺乳期小鼠进行了呼吸道感染的自然史建模。

方法

成年和哺乳期 Balb/c 小鼠经鼻腔感染,并评估疾病的剂量反应以及病毒在肺部和其他器官中的复制情况。通过免疫荧光和组织切片的 HRP 染色评估病毒抗原,通过福尔马林固定、H+E 染色的组织切片评估组织病理学。

结果

成年小鼠鼻腔感染高剂量(10(7) pfu)T1L 会导致致命的呼吸窘迫,但 T3D 不会。相反,T1L 和 T3D 均以中等病毒剂量(10(5) pfu)杀死哺乳期小鼠,但临床症状不同,T1L 引起呼吸衰竭,T3D 引起脑炎。感染引起短暂的病毒血症,导致病毒扩散到外周组织,疾病与病毒复制和病理学相关。肺部病毒抗原的免疫荧光染色显示呼肠孤病毒感染主要与肺泡有关,支气管上皮的参与较少。脑组织中病毒抗原的免疫荧光和 HRP 染色显示 T3D 感染神经元,T1L 感染神经胶质细胞。

结论

这些呼肠孤病毒呼吸道感染的小鼠模型表现出与年龄和品系相关的疾病,预计对理解和调节人类自然和治疗性呼肠孤病毒感染具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a35/3605257/3a4a24b5fbd3/1743-422X-10-67-1.jpg

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