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dc.contributor.authorCorona, Abigail
dc.date.accessioned2020-01-14T20:29:08Z
dc.date.available2020-01-14T20:29:08Z
dc.date.issued2019en_US
dc.identifier.urihttp://hdl.handle.net/10713/11615
dc.description2019
dc.descriptionMolecular Microbiology and Immunology
dc.descriptionUniversity of Maryland, Baltimore
dc.descriptionPh.D.
dc.description.abstractEnterovirus-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.
dc.subjectVirology
dc.subjectCellular biology
dc.subjectamphisomeen_US
dc.subjectpicornavirusen_US
dc.subjectSNAP29en_US
dc.subjectSNAP47en_US
dc.subject.meshAutophagyen_US
dc.subject.meshEnterovirus D, Humanen_US
dc.subject.meshPicornaviridaeen_US
dc.titleThe Roles of Autophagic SNARE proteins SNAP29 and SNAP47 in Autophagy and Enterovirus D68 Replicationen_US
dc.typedissertationen_US
dc.date.updated2020-01-08T23:01:34Z
dc.language.rfc3066en
dc.contributor.advisorJackson, William T.
dc.contributor.orcid0000-0003-2271-4541en_US
refterms.dateFOA2020-01-14T20:29:09Z


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