Interactions between ocular tissue and RSV

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DESCRIPTION (provided by applicant): The goal of this research is to investigate the interaction between the eye and respiratory syncytial virus (RSV), a clinically significant pathogen of the respiratory tract. Infection by RSV, a RNA virus of the Paramyxoviridae family, produces bronchopulmonary dysplasia, destruction of lung cells, asthma, and results in an annual death toll of roughly 1 million, mostly infants. Thus, RSV is traditionally considered a respiratory pathogen. However, there is no comprehensive knowledge about the exact pathway(s) of entry of the virus into the lung in natural infection. More than a decade ago, indirect epidemiological studies suggested that the eye might play a role in the respiratory RSV disease. In recent times, studies from our laboratory and others' have established a significant association between allergic conjunctivitis and the presence of RSV and cytokines in the eye. Thus, we believe that the time is right to test whether the eye may be an important organ and route of RSV-infection. Based on this, we will test the following hypothesis:(i) The eye serves as a bona fide physiological organ that supports RSV infection; (ii) in this capacity, the eye provides a gateway through which RSV gains entry, and eventually proceeds to infect the lungs; (iii) RSV-infection of the eye leads to the elaboration of immunoregulatory cytokines/ chemokines, which may be an important cause of "Allergy Eye" (Red Eye), commonly seen in patients with respiratory disease. Our studies of ocular RSV infection will use the mouse model, well established for RSV-mediated respiratory infection that faithfully mimics the human respiratory disease. Should our hypotheses be proven, it would establish an animal model for RSV-eye interaction, and open new directions in ocular immunopathology, RNA virus-activated signaling pathways in the eye, and antiviral drug regimen targeting the eye