Respiratory Syncytial (RS) Virus, a member of the paramyxovirus family which contains many human and animal pathogens, is a leading cause of serious pediatric respiratory disease. Natural infection with RS virus affords only partial protection and repeated infections are frequent. The RS virus RNA genome has 10 genes encoding 10 viral proteins. Four of these RS virus proteins have no direct counterparts among other paramyxovirus proteins and the overall structural features of the attachment protein G are unlike those of any known viral membrane protein. The relationship between the distinctive molecular features of RS virus and its unusual pathogenesis is unknown. The purpose of the work outlined here is to provide a concerted study of the structure and biological function of the distinctive RS virus gene products in order to understand their roles both in virus infection and in the immune response to the virus.
The specific aims of the grant are as follows: 1. Analyse the role of individual structural features of the polypeptide backbone of G in synthesis, maturation and transport. 2. Analyze RS virus and RS virus G protein maturation in polarized cells. 3. Analyze the role of carbohydrate in the synthesis, maturation and transport of G. 4. Analyze the role of carbohydrate in the biological function of G. 5. Analyze the effect of carbohydrate on the immune response to G. 6. Characterize the structure of G by chemical and biophysical means. 7. Identify and analyze regions of G important in biological function. 8. Examine the function of the RS nonstructural proteins 1B and 1C, and the 1A and 22K proteins. 9. Examine the role of the nonstructural proteins and the 1A and 22K proteins in infection and in cell mediated immune responses.
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