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Title: Pseudorabies Virus Infection Induces Targeted Degradation of the Kinesin-3 Motor KIF1A
Authors: Huang, Hao
Advisors: Enquist, Lynn W
Contributors: Molecular Biology Department
Keywords: alphaherpesvirus
axonal sorting
proteasomal degradation
pseudorabies virus
Subjects: Virology
Molecular biology
Issue Date: 2019
Publisher: Princeton, NJ : Princeton University
Abstract: Alphaherpesviruses, including Pseudorabies Virus (PRV), are neuroinvasive pathogens that establish life-long latency in peripheral ganglia following the initial infection at mucosal surfaces. The establishment of latent infection and the subsequent reactivation during which newly-assembled virions are sorted into and transported anterogradely inside axons to the initial mucosal site of infection, relies heavily on axonal bidirectional transport mediated by microtubule-based motors. Previous studies using cultured peripheral nervous system (PNS) neurons have demonstrated that KIF1A, a Kinesin-3 motor, mediates the efficient axonal sorting and transport of newly-assembled PRV virions. In this study, we report that KIF1A, unlike other axonal kinesins, is an intrinsically unstable protein prone to proteasomal degradation. Furthermore, PRV infection of neuronal cells induces a targeted degradation of KIF1A protein. We propose that the specific depletion of KIF1A proteins stems from not only an non-specific depletion of KIF1A mRNA but also targeted degradation of KIF1A proteins during PRV infection. Using a series of PRV mutants deficient in axonal sorting and anterograde spread, we identified the PRV US9/gE/gI protein complex as a viral factor facilitating the proteasomal degradation of KIF1A proteins. Moreover, using compartmented neuronal culture that fluidically and physically separates axons from cell bodies, we found that the proteasomal degradation of KIF1A proteins occurs in axons. We propose that PRV anterograde sorting complex, gE/gI/US9, recruits KIF1A to viral transport vesicles for axonal sorting and transport, and eventually promotes the proteasomal degradation of KIF1A in axons.
Alternate format: The Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the library's main catalog:
Type of Material: Academic dissertations (Ph.D.)
Language: en
Appears in Collections:Molecular Biology

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