Bitko Vira, Musiyenko Alla, Barik Sailen
Department of Biochemistry and Molecular Biology (MSB 2370), University of South Alabama, College of Medicine, 307 University Blvd., Mobile, AL 36688-0002, USA.
J Virol. 2007 Jan;81(2):783-90. doi: 10.1128/JVI.01437-06. Epub 2006 Oct 18.
Respiratory syncytial virus (RSV) is the foremost respiratory pathogen in newborns and claims millions of lives annually. However, there has been no methodical study of the pathway(s) of entry of RSV or its interaction with nonrespiratory tissues. We and others have recently established a significant association between allergic conjunctivitis and the presence of RSV in the eye. Here we adopt a BALB/c mouse model and demonstrate that when instilled in the live murine eye, RSV not only replicated robustly in the eye but also migrated to the lung and produced a respiratory disease that is indistinguishable from the standard, nasally acquired RSV disease. Ocularly applied synthetic anti-RSV small interfering RNA prevented infection of the eye as well as the lung. RSV infection of the eye activated a plethora of ocular cytokines and chemokines with profound relevance to inflammation of the eye. Anticytokine treatments in the eye reduced ocular inflammation but had no effect on viral growth in both eye and lung, demonstrating a role of the cytokine response in ocular pathology. These results establish the eye as a major gateway of respiratory infection and a respiratory virus as a bona fide eye pathogen, thus offering novel intervention and treatment options.
呼吸道合胞病毒（RSV）是新生儿最重要的呼吸道病原体，每年导致数百万人死亡。然而，尚未对RSV的进入途径或其与非呼吸组织的相互作用进行系统研究。我们和其他人最近发现过敏性结膜炎与眼部RSV的存在之间存在显著关联。在此，我们采用BALB/c小鼠模型，证明当将RSV滴入活鼠眼内时，它不仅在眼中大量复制，还迁移至肺部并引发一种与标准经鼻感染的RSV疾病难以区分的呼吸道疾病。眼部应用合成抗RSV小干扰RNA可预防眼部和肺部感染。眼部RSV感染激活了大量与眼部炎症密切相关的眼部细胞因子和趋化因子。眼部抗细胞因子治疗可减轻眼部炎症，但对眼和肺中的病毒生长均无影响，这表明细胞因子反应在眼部病理中起作用。这些结果确立了眼睛作为呼吸道感染的主要门户以及呼吸道病毒作为真正的眼部病原体，从而提供了新的干预和治疗选择。
