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Two Modes of the Axonal Interferon Response Limit Alphaherpesvirus Neuroinvasion
Infection by alphaherpesviruses, including herpes simplex virus (HSV) and pseudorabies virus (PRV), typically begins at epithelial surfaces and continues into the peripheral nervous system (PNS). Inflammatory responses are induced at the infected peripheral site prior to invasion of the PNS. When th...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Microbiology
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742712/ https://www.ncbi.nlm.nih.gov/pubmed/26838720 http://dx.doi.org/10.1128/mBio.02145-15 |
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author | Song, Ren Koyuncu, Orkide O. Greco, Todd M. Diner, Benjamin A. Cristea, Ileana M. Enquist, Lynn W. |
author_facet | Song, Ren Koyuncu, Orkide O. Greco, Todd M. Diner, Benjamin A. Cristea, Ileana M. Enquist, Lynn W. |
author_sort | Song, Ren |
collection | PubMed |
description | Infection by alphaherpesviruses, including herpes simplex virus (HSV) and pseudorabies virus (PRV), typically begins at epithelial surfaces and continues into the peripheral nervous system (PNS). Inflammatory responses are induced at the infected peripheral site prior to invasion of the PNS. When the peripheral tissue is first infected, only the innervating axons are exposed to this inflammatory milieu, which includes the interferons (IFNs). The fundamental question is how do PNS cell bodies respond to these distant, potentially damaging events experienced by axons. Using compartmented cultures that physically separate neuron axons from cell bodies, we found that pretreating isolated axons with beta interferon (IFN-β) or gamma interferon (IFN-γ) significantly diminished the number of herpes simplex virus 1 (HSV-1) and PRV particles moving in axons toward the cell bodies in a receptor-dependent manner. Exposing axons to IFN-β induced STAT1 phosphorylation (p-STAT1) only in axons, while exposure of axons to IFN-γ induced p-STAT1 accumulation in distant cell body nuclei. Blocking transcription in cell bodies eliminated antiviral effects induced by IFN-γ, but not those induced by IFN-β. Proteomic analysis of IFN-β- or IFN-γ-treated axons identified several differentially regulated proteins. Therefore, unlike treatment with IFN-γ, IFN-β induces a noncanonical, local antiviral response in axons. The activation of a local IFN response in axons represents a new paradigm for cytokine control of neuroinvasion. |
format | Online Article Text |
id | pubmed-4742712 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | American Society of Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-47427122016-02-13 Two Modes of the Axonal Interferon Response Limit Alphaherpesvirus Neuroinvasion Song, Ren Koyuncu, Orkide O. Greco, Todd M. Diner, Benjamin A. Cristea, Ileana M. Enquist, Lynn W. mBio Research Article Infection by alphaherpesviruses, including herpes simplex virus (HSV) and pseudorabies virus (PRV), typically begins at epithelial surfaces and continues into the peripheral nervous system (PNS). Inflammatory responses are induced at the infected peripheral site prior to invasion of the PNS. When the peripheral tissue is first infected, only the innervating axons are exposed to this inflammatory milieu, which includes the interferons (IFNs). The fundamental question is how do PNS cell bodies respond to these distant, potentially damaging events experienced by axons. Using compartmented cultures that physically separate neuron axons from cell bodies, we found that pretreating isolated axons with beta interferon (IFN-β) or gamma interferon (IFN-γ) significantly diminished the number of herpes simplex virus 1 (HSV-1) and PRV particles moving in axons toward the cell bodies in a receptor-dependent manner. Exposing axons to IFN-β induced STAT1 phosphorylation (p-STAT1) only in axons, while exposure of axons to IFN-γ induced p-STAT1 accumulation in distant cell body nuclei. Blocking transcription in cell bodies eliminated antiviral effects induced by IFN-γ, but not those induced by IFN-β. Proteomic analysis of IFN-β- or IFN-γ-treated axons identified several differentially regulated proteins. Therefore, unlike treatment with IFN-γ, IFN-β induces a noncanonical, local antiviral response in axons. The activation of a local IFN response in axons represents a new paradigm for cytokine control of neuroinvasion. American Society of Microbiology 2016-02-02 /pmc/articles/PMC4742712/ /pubmed/26838720 http://dx.doi.org/10.1128/mBio.02145-15 Text en Copyright © 2016 Song et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Song, Ren Koyuncu, Orkide O. Greco, Todd M. Diner, Benjamin A. Cristea, Ileana M. Enquist, Lynn W. Two Modes of the Axonal Interferon Response Limit Alphaherpesvirus Neuroinvasion |
title | Two Modes of the Axonal Interferon Response Limit Alphaherpesvirus Neuroinvasion |
title_full | Two Modes of the Axonal Interferon Response Limit Alphaherpesvirus Neuroinvasion |
title_fullStr | Two Modes of the Axonal Interferon Response Limit Alphaherpesvirus Neuroinvasion |
title_full_unstemmed | Two Modes of the Axonal Interferon Response Limit Alphaherpesvirus Neuroinvasion |
title_short | Two Modes of the Axonal Interferon Response Limit Alphaherpesvirus Neuroinvasion |
title_sort | two modes of the axonal interferon response limit alphaherpesvirus neuroinvasion |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742712/ https://www.ncbi.nlm.nih.gov/pubmed/26838720 http://dx.doi.org/10.1128/mBio.02145-15 |
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