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dc.contributor.advisorEnquist, Lynn W
dc.contributor.authorEsteves, Andrew
dc.contributor.otherMolecular Biology Department
dc.description.abstractInfection of peripheral axons of the sensory and autonomic neurons by alphaherpes viruses is a critical stage in establishing a life-long infection in the host. Upon entering the cytoplasm, herpes virus nucleocapsids and inner-tegument proteins must engage the cellular retrograde transport machinery to promote the long-distance movement of the virion components to the nucleus. The current model outlining this process is incomplete and further investigation is required to discover all viral and cellular determinants involved as well as the temporality of the events. Using a modified Campenot tri-chamber system and embryonic rat superior cervical ganglia neurons to replicate axonal infection by alphaherpes viruses and subsequent long-distance transport of virion particles I have discovered a novel role of the pseudorabies virus (PRV) serine/threonine kinase, US3, in promoting efficient retrograde transport of nucleocapsids. I discovered that transporting nucleocapsids move at similar velocities both in the presence and absence of a functional US3 kinase, however fewer nucleocapsids overall transport when US3 is not present and move for shorter periods of time before stopping, suggesting US3 is required for nucleocapsid engagement with the retrograde transport machinery. Fewer PRV nucleocapsids reach the cell bodies and lead to a productive infection 12 hours post infection (hpi) when US3 is absent. Furthermore, US3 was responsible for the induction of local translation in axons as early as 1hpi through the stimulation of a PI3K/Akt-mToRC1 signaling pathway. Preliminary evidence was provided showing phosphorylation of cytoplasmic dynein intermediate chain occurred during PRV infection and was dependent on US3, Akt phosphorylation and axonal translation. These data describe a novel role for US3 in nucleocapsid engagement with dynein and characterize the cellular signaling pathway used to mediate PRV-induced translation in axons.
dc.publisherPrinceton, NJ : Princeton University
dc.relation.isformatofThe Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the library's main catalog: <a href=></a>
dc.subjectAlphaherpes virus
dc.subjectmRNA Translation
dc.subjectPseudorabies virus
dc.subjectRetrograde Transport
dc.subject.classificationCellular biology
dc.titleA pseudorabies virus serine/threonine kinase, US3, promotes retrograde transport in axons via Akt/mToRC1 signaling
dc.typeAcademic dissertations (Ph.D.)
pu.departmentMolecular Biology
Appears in Collections:Molecular Biology

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