Viral infection of the lungs through the eye.
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.
Bitko
Vira
V
Department of Biochemistry and Molecular Biology (MSB 2370), University of South Alabama, College of Medicine, 307 University Blvd., Mobile, AL 36688-0002, USA.
Musiyenko
Alla
A
Barik
Sailen
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D003236:Conjunctivitis, Viral / Q000628:therapy / Q000635:transmission* / Q000821:virology*; D004195:Disease Models, Animal; D005123:Eye / Q000276:immunology / Q000821:virology*; D005260:Female; D006801:Humans; D053582:Interleukin-1alpha / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000628:therapy / Q000635:transmission* / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology; D012141:Respiratory Tract Infections / Q000628:therapy / Q000821:virology*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D053582:Interleukin-1alpha; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha