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dc.contributor.advisorBullitt, Estheren_US
dc.contributor.authorYang, Jie Euneen_US
dc.date.accessioned2018-07-17T14:27:01Z
dc.date.issued2018
dc.identifier.urihttps://hdl.handle.net/2144/29955
dc.description.abstractWhile enteroviruses, including poliovirus, are conventionally released upon cell lysis, recent studies show that phosphatidylserine-enriched infectious extracellular vesicles (IEVs) shed by infected cells can transport clusters of enteroviruses from cell to cell, resulting in increased infectivity. Combining structural and biochemical analyses, we focused on IEVs shed from poliovirus-infected cells, a classical prototype for studying enteroviruses. Transmission cryo-electron microscopy, cryo-electron tomography and computational reconstruction, present the first three-dimensional structures of well-preserved IEVs and purified exosomes. We observed that single-membraned IEVs present a wide size range in diameter. Clusters of virions can be either densely packed within a protein-coated irregularly shaped IEV, or concentrated at one or both ends of an IEV, forming a polar structure. In addition to virions, IEVs often contain internal vesicles, “ramen-noodle”-like structures with strong density, and partially assembled virion-like structures. Viral replication complex components, including viral proteins polymerase 3D, 3CD, 3A, 3AB, 2BC, 2C and (+) and (-) stranded RNAs were detected in IEVs. Furthermore, (-) stranded RNA templates are protected by the IEVs, not packed in viral capsids. The transported viral replication components (viral proteins and RNAs) and virions within IEVs initiate a stronger and faster viral replication in recipient cells than free virions. Both cryo-electron tomographic and mass spectrometry data also showed that virions and “ramen-noodle”-like structures were also observed in purified CD9 positive exosomes from poliovirus-infected cells. Viral protein 3AB, detected on the membrane of IEVs, can invaginate membranous structures to engulf large proteins into a closed lumen. Our study demonstrates that IEVs can transport viral replication complex components to initiate a rapid onset of viral replication, as part of a novel viral transmission mechanism. Viral protein 3AB may contribute to forming IEVs throughout the infection.en_US
dc.language.isoen_US
dc.subjectBiophysicsen_US
dc.subjectEnterovirusen_US
dc.subjectExosomeen_US
dc.subjectTransmissionen_US
dc.subjectExtracellular vesiclesen_US
dc.titleExploration of a novel non-lytic viral transmission mechanism utilized by a non-enveloped positive-sense RNA virusen_US
dc.typeThesis/Dissertationen_US
dc.date.updated2018-06-12T22:12:54Z
dc.description.embargo2019-06-12T00:00:00Z
etd.degree.nameDoctor of Philosophyen_US
etd.degree.leveldoctoralen_US
etd.degree.disciplineBiophysicsen_US
etd.degree.grantorBoston Universityen_US


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