Herpes Simplex Virus 1 (HSV-1) Infected Cell Protein 0 (ICP0) Targets of Ubiquitination during Productive Infection of Primary Adult Sensory Neurons

dc.contributor.authorHarrell, Telvin L.en
dc.contributor.authorDavido, David J.en
dc.contributor.authorBertke, Andrea S.en
dc.date.accessioned2023-02-10T14:46:08Zen
dc.date.available2023-02-10T14:46:08Zen
dc.date.issued2023-02-02en
dc.date.updated2023-02-10T14:28:48Zen
dc.description.abstractHerpes simplex virus 1 (HSV-1) enters sensory neurons with the potential for productive or latent infection. For either outcome, HSV-1 must curtail the intrinsic immune response, regulate viral gene expression, and remove host proteins that could restrict viral processes. Infected cell protein 0 (ICP0), a virus-encoded E3 ubiquitin ligase, supports these processes by mediating the transfer of ubiquitin to target proteins to change their location, alter their function, or induce their degradation. To identify ubiquitination targets of ICP0 during productive infection in sensory neurons, we immunoprecipitated ubiquitinated proteins from primary adult sensory neurons infected with HSV-1 KOS (wild-type), HSV-1 <i>n</i>212 (expressing truncated, defective ICP0), and uninfected controls using anti-ubiquitin antibody FK2 (recognizing K29, K48, K63 and monoubiquitinated proteins), followed by LC-MS/MS and comparative analyses. We identified 40 unique proteins ubiquitinated by ICP0 and 17 ubiquitinated by both ICP0 and host mechanisms, of which High Mobility Group Protein I/Y (HMG I/Y) and TAR DNA Binding Protein 43 (TDP43) were selected for further analysis. We show that ICP0 ubiquitinates HMG I/Y and TDP43, altering protein expression at specific time points during productive HSV-1 infection, demonstrating that ICP0 manipulates the sensory neuronal environment in a time-dependent manner to regulate infection outcome in neurons.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationHarrell, T.L.; Davido, D.J.; Bertke, A.S. Herpes Simplex Virus 1 (HSV-1) Infected Cell Protein 0 (ICP0) Targets of Ubiquitination during Productive Infection of Primary Adult Sensory Neurons. Int. J. Mol. Sci. 2023, 24, 2931.en
dc.identifier.doihttps://doi.org/10.3390/ijms24032931en
dc.identifier.urihttp://hdl.handle.net/10919/113783en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectHSVen
dc.subjecthuman herpes virusen
dc.subjectalphaherpesvirusen
dc.subjectICP0en
dc.subjectmass spectrometryen
dc.subjectprimary neuronsen
dc.subjectHMG I/Yen
dc.subjectHigh Mobility Group Protein I/Yen
dc.subjectTDP43en
dc.subjectTAR DNA Binding Protein 43en
dc.titleHerpes Simplex Virus 1 (HSV-1) Infected Cell Protein 0 (ICP0) Targets of Ubiquitination during Productive Infection of Primary Adult Sensory Neuronsen
dc.title.serialInternational Journal of Molecular Scienceen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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