Mejías Asunción, Chávez-Bueno Susana, Jafri Hasan S, Ramilo Octavio
Division of Pediatric Infectious Diseases, The University of Texas Southwestern Medical Center and Children's Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Pediatr Infect Dis J. 2005 Nov;24(11 Suppl):S189-96, discussion S196-7. doi: 10.1097/01.inf.0000188196.87969.9a.
Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and pneumonia among children aged < 1 year. The majority of children hospitalized for RSV infection are younger than 6 months of age. RSV also causes repeated infections including severe lower respiratory tract disease, which may occur at any age, especially among the elderly or those with compromised cardiac, pulmonary, or immune systems.
Using the mouse model of RSV infection, this article examines the immunopathogenesis during acute and chronic phases of the disease. This model allows for measurement of basal enhanced pause, which reflects airway obstruction in the acute phase, and the response to methacholine challenge to assess airway hyperresponsiveness during the chronic phase. This article also summarizes some recent studies focusing on novel perspectives and strategies for treatment and prevention of RSV infections.
Compared with the lungs of sham-inoculated control mice, mice inoculated with live RSV showed a persistent progression of the severity of pneumonia as determined by an increasing histopathologic score. Mucus production of RSV-infected mice in the acute phase illustrated increased periodic acid-Schiff-positive hypertrophic cells in central and peripheral airways.
RSV-infected mice with persistent airway hyperresponsiveness exhibited the presence of abnormal chronic inflammatory changes and mucus overproduction, which likely contributed to long term airway disease induced by RSV infection. These findings provide a histologic correlation to the abnormal pulmonary responses documented by plethysmography. Current trials have demonstrated positive results in continuing to target different alternatives for a new RSV vaccine.
呼吸道合胞病毒(RSV)是1岁以下儿童毛细支气管炎和肺炎的最常见病因。因RSV感染住院的大多数儿童年龄小于6个月。RSV还会引发反复感染,包括严重的下呼吸道疾病,可发生于任何年龄,尤其是老年人或心脏、肺部或免疫系统受损者。
本文利用RSV感染的小鼠模型,研究了该疾病急性和慢性阶段的免疫发病机制。该模型可测量基础增强呼吸暂停,其反映急性期的气道阻塞情况,还可测量对乙酰甲胆碱激发试验的反应,以评估慢性期的气道高反应性。本文还总结了一些近期研究,这些研究聚焦于RSV感染治疗和预防的新观点和新策略。
与假接种对照小鼠的肺部相比,接种活RSV的小鼠肺炎严重程度持续进展,这可通过组织病理学评分增加来确定。急性期RSV感染小鼠的黏液分泌表明,中央和外周气道中高碘酸-希夫染色阳性的肥大细胞增多。
具有持续性气道高反应性的RSV感染小鼠表现出异常的慢性炎症变化和黏液过度产生,这可能导致RSV感染引起的长期气道疾病。这些发现为体积描记法记录的异常肺部反应提供了组织学关联。目前的试验已证明,继续针对新型RSV疫苗的不同替代方案取得了积极成果。