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Title page for ETD etd-05232012-163316


Type of Document Dissertation
Author Shaikh, Fyza Yusuf
Author's Email Address fyza.shaikh@vanderbilt.edu
URN etd-05232012-163316
Title The role of the respiratory syncytial virus fusion protein in viral filamentous assembly
Degree PhD
Department Microbiology and Immunology
Advisory Committee
Advisor Name Title
Terence Dermody Committee Chair
Andrew Link Committee Member
Anne Kenworthy Committee Member
Christopher Aiken Committee Member
James Crowe Committee Member
Todd Graham Committee Member
Keywords
  • filaments
  • cytoplasmic tail
  • paramyxovirus
  • respiratory syncytial virus
  • fusion protein
  • assembly and budding
Date of Defense 2012-05-01
Availability unrestricted
Abstract
Respiratory syncytial virus (RSV) is a single-stranded RNA virus in the Paramyxoviridae family that is a leading cause of pneumonia and bronchiolitis in infants and the elderly. RSV preferentially assembles and buds from the apical surface of polarized epithelial cells, forming filamentous structures that contain both viral proteins and the genomic RNA. The experiments described in this thesis were designed to identify the host and viral determinants of RSV assembly and budding. First, I show that viral filaments are the likely sites of viral assembly at the cell surface. Interestingly, these data also show that viral filaments are formed by selective sorting of viral proteins into filaments and the exclusion of host cytosolic and membrane proteins. Second, I identify viral determinants of filamentous assembly by showing that a specific phenylalanine amino acid in the fusion protein cytoplasmic tail is necessary for incorporation of internal virion proteins into virus-like filaments. Furthermore, the same phenylalanine residue was shown to be important for incorporation of internal virion proteins into virus-like particles, indicating that the phenylalanine residue is required for both assembly and budding. Finally, I discuss the viral interactions with the host cell as explored by yeast two-hybrid screens. The data show that a number of host proteins localize to viral structures, but none are essential for viral replication. Collectively, these studies suggest that the fusion protein cytoplasmic tail is critical for virus assembly and that viral proteins are the driving factors in RSV assembly and budding.
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