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Viral modulation of type II interferon increases T cell adhesion and virus spread

During primary infection, varicella zoster virus (VZV) infects epithelial cells in the respiratory lymphoid organs and mucosa. Subsequent infection of lymphocytes, T cells in particular, causes primary viremia allowing systemic spread throughout the host, including the skin. This results in the expr...

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Autores principales: Jürgens, Carina, Ssebyatika, George, Beyer, Sarah, Plückebaum, Nina, Kropp, Kai A., González-Motos, Víctor, Ritter, Birgit, Böning, Heike, Nikolouli, Eirini, Kinchington, Paul R., Lachmann, Nico, Depledge, Daniel Pearce, Krey, Thomas, Viejo-Borbolla, Abel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10246016/
https://www.ncbi.nlm.nih.gov/pubmed/37292914
http://dx.doi.org/10.1101/2023.05.26.542397
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author Jürgens, Carina
Ssebyatika, George
Beyer, Sarah
Plückebaum, Nina
Kropp, Kai A.
González-Motos, Víctor
Ritter, Birgit
Böning, Heike
Nikolouli, Eirini
Kinchington, Paul R.
Lachmann, Nico
Depledge, Daniel Pearce
Krey, Thomas
Viejo-Borbolla, Abel
author_facet Jürgens, Carina
Ssebyatika, George
Beyer, Sarah
Plückebaum, Nina
Kropp, Kai A.
González-Motos, Víctor
Ritter, Birgit
Böning, Heike
Nikolouli, Eirini
Kinchington, Paul R.
Lachmann, Nico
Depledge, Daniel Pearce
Krey, Thomas
Viejo-Borbolla, Abel
author_sort Jürgens, Carina
collection PubMed
description During primary infection, varicella zoster virus (VZV) infects epithelial cells in the respiratory lymphoid organs and mucosa. Subsequent infection of lymphocytes, T cells in particular, causes primary viremia allowing systemic spread throughout the host, including the skin. This results in the expression of cytokines, including interferons (IFNs) which partly limit primary infection. VZV also spreads from skin keratinocytes to lymphocytes prior to secondary viremia. How VZV infects lymphocytes from epithelial cells while evading the cytokine response has not been fully established. Here, we show that VZV glycoprotein C (gC) binds IFN-γ and modifies its activity. Transcriptomic analysis revealed that gC in combination with IFN-γ increased the expression of a small subset of IFN-stimulated genes (ISGs), including intercellular adhesion molecule 1 (ICAM1), as well as several chemokines and immunomodulatory genes. The higher ICAM1 protein level at the plasma membrane of epithelial cells resulted in lymphocyte function-associated antigen 1 (LFA-1)-dependent T cell adhesion. This gC activity required a stable interaction with IFN-γ and signalling through the IFN-γ receptor. Finally, the presence of gC during infection increased VZV spread from epithelial cells to peripheral blood mononuclear cells. This constitutes the discovery of a novel strategy to modulate the activity of IFN-γ, inducing the expression of a subset of ISGs, leading to enhanced T cell adhesion and virus spread.
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spelling pubmed-102460162023-06-08 Viral modulation of type II interferon increases T cell adhesion and virus spread Jürgens, Carina Ssebyatika, George Beyer, Sarah Plückebaum, Nina Kropp, Kai A. González-Motos, Víctor Ritter, Birgit Böning, Heike Nikolouli, Eirini Kinchington, Paul R. Lachmann, Nico Depledge, Daniel Pearce Krey, Thomas Viejo-Borbolla, Abel bioRxiv Article During primary infection, varicella zoster virus (VZV) infects epithelial cells in the respiratory lymphoid organs and mucosa. Subsequent infection of lymphocytes, T cells in particular, causes primary viremia allowing systemic spread throughout the host, including the skin. This results in the expression of cytokines, including interferons (IFNs) which partly limit primary infection. VZV also spreads from skin keratinocytes to lymphocytes prior to secondary viremia. How VZV infects lymphocytes from epithelial cells while evading the cytokine response has not been fully established. Here, we show that VZV glycoprotein C (gC) binds IFN-γ and modifies its activity. Transcriptomic analysis revealed that gC in combination with IFN-γ increased the expression of a small subset of IFN-stimulated genes (ISGs), including intercellular adhesion molecule 1 (ICAM1), as well as several chemokines and immunomodulatory genes. The higher ICAM1 protein level at the plasma membrane of epithelial cells resulted in lymphocyte function-associated antigen 1 (LFA-1)-dependent T cell adhesion. This gC activity required a stable interaction with IFN-γ and signalling through the IFN-γ receptor. Finally, the presence of gC during infection increased VZV spread from epithelial cells to peripheral blood mononuclear cells. This constitutes the discovery of a novel strategy to modulate the activity of IFN-γ, inducing the expression of a subset of ISGs, leading to enhanced T cell adhesion and virus spread. Cold Spring Harbor Laboratory 2023-05-26 /pmc/articles/PMC10246016/ /pubmed/37292914 http://dx.doi.org/10.1101/2023.05.26.542397 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Jürgens, Carina
Ssebyatika, George
Beyer, Sarah
Plückebaum, Nina
Kropp, Kai A.
González-Motos, Víctor
Ritter, Birgit
Böning, Heike
Nikolouli, Eirini
Kinchington, Paul R.
Lachmann, Nico
Depledge, Daniel Pearce
Krey, Thomas
Viejo-Borbolla, Abel
Viral modulation of type II interferon increases T cell adhesion and virus spread
title Viral modulation of type II interferon increases T cell adhesion and virus spread
title_full Viral modulation of type II interferon increases T cell adhesion and virus spread
title_fullStr Viral modulation of type II interferon increases T cell adhesion and virus spread
title_full_unstemmed Viral modulation of type II interferon increases T cell adhesion and virus spread
title_short Viral modulation of type II interferon increases T cell adhesion and virus spread
title_sort viral modulation of type ii interferon increases t cell adhesion and virus spread
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10246016/
https://www.ncbi.nlm.nih.gov/pubmed/37292914
http://dx.doi.org/10.1101/2023.05.26.542397
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