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    The Roles of Autophagic SNARE proteins SNAP29 and SNAP47 in Autophagy and Enterovirus D68 Replication

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    Author
    Corona, Abigail cc
    0000-0003-2271-4541
    Advisor
    Jackson, William T.
    Date
    2019
    Type
    dissertation
    
    Metadata
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    Abstract
    Enterovirus-D68 (EV-D68) is a positive-sense, single-stranded RNA virus of the Picornaviridae family that causes respiratory disease in children and has been implicated in recent outbreaks of acute flaccid myelitis, a severe paralysis syndrome. We have demonstrated that EV-D68 induces autophagy upon infection and modifies the autophagic process to benefit its own replication. Autophagy is a regulated process of cytosolic degradation in eukaryotic cells which maintains cellular homeostasis by degrading damaged organelles, protein aggregates, microbes and other xenobiotics in the cytoplasm. The autophagic process is characterized by the formation of double-membraned autophagosomes around cytosolic cargo, which then undergo a series of fusion steps with endosomes and lysosomes to degrade the vesicle’s contents. The autophagy pathway is targeted by many pathogens, either to protect themselves from degradation or to utilize components to benefit replication. EV-D68 uses virally-encoded proteases to cleave an autophagosome fusion SNARE protein, SNAP29, blocking delivery of autophagosome contents, including nascent viruses, to the lysosome. Our data show that relocalization occurs for SNAP47 during autophagy induction, and is required for normal virus replication. SNAP47 plays a major role in acidification of autophagosomes into amphisomes, with binding partner VAMP7, which we hypothesize promotes maturation of virions into infectious particles. Using both viral- and non-viral forms of autophagy induction, these data suggest that the cellular network of SNARE proteins is being redirected during infection to promote EV-D68 replication and egress from the cell.
    Description
    2019
    Molecular Microbiology and Immunology
    University of Maryland, Baltimore
    Ph.D.
    Keyword
    Virology
    Cellular biology
    amphisome
    picornavirus
    SNAP29
    SNAP47
    Autophagy
    Enterovirus D, Human
    Picornaviridae
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/11615
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    Theses and Dissertations School of Medicine
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