Differential T cell response against BK virus regulatory and structural antigens: A viral dynamics modelling approach

BK virus (BKV) associated nephropathy affects 1–10% of kidney transplant recipients, leading to graft failure in about 50% of cases. Immune responses against different BKV antigens have been shown to have a prognostic value for disease development. Data currently suggest that the structural antigens...

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Autores principales: Blazquez-Navarro, Arturo, Schachtner, Thomas, Stervbo, Ulrik, Sefrin, Anett, Stein, Maik, Westhoff, Timm H., Reinke, Petra, Klipp, Edda, Babel, Nina, Neumann, Avidan U., Or-Guil, Michal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944912/
https://www.ncbi.nlm.nih.gov/pubmed/29746472
http://dx.doi.org/10.1371/journal.pcbi.1005998
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author Blazquez-Navarro, Arturo
Schachtner, Thomas
Stervbo, Ulrik
Sefrin, Anett
Stein, Maik
Westhoff, Timm H.
Reinke, Petra
Klipp, Edda
Babel, Nina
Neumann, Avidan U.
Or-Guil, Michal
author_facet Blazquez-Navarro, Arturo
Schachtner, Thomas
Stervbo, Ulrik
Sefrin, Anett
Stein, Maik
Westhoff, Timm H.
Reinke, Petra
Klipp, Edda
Babel, Nina
Neumann, Avidan U.
Or-Guil, Michal
author_sort Blazquez-Navarro, Arturo
collection PubMed
description BK virus (BKV) associated nephropathy affects 1–10% of kidney transplant recipients, leading to graft failure in about 50% of cases. Immune responses against different BKV antigens have been shown to have a prognostic value for disease development. Data currently suggest that the structural antigens and regulatory antigens of BKV might each trigger a different mode of action of the immune response. To study the influence of different modes of action of the cellular immune response on BKV clearance dynamics, we have analysed the kinetics of BKV plasma load and anti-BKV T cell response (Elispot) in six patients with BKV associated nephropathy using ODE modelling. The results show that only a small number of hypotheses on the mode of action are compatible with the empirical data. The hypothesis with the highest empirical support is that structural antigens trigger blocking of virus production from infected cells, whereas regulatory antigens trigger an acceleration of death of infected cells. These differential modes of action could be important for our understanding of BKV resolution, as according to the hypothesis, only regulatory antigens would trigger a fast and continuous clearance of the viral load. Other hypotheses showed a lower degree of empirical support, but could potentially explain the clearing mechanisms of individual patients. Our results highlight the heterogeneity of the dynamics, including the delay between immune response against structural versus regulatory antigens, and its relevance for BKV clearance. Our modelling approach is the first that studies the process of BKV clearance by bringing together viral and immune kinetics and can provide a framework for personalised hypotheses generation on the interrelations between cellular immunity and viral dynamics.
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spelling pubmed-59449122018-05-18 Differential T cell response against BK virus regulatory and structural antigens: A viral dynamics modelling approach Blazquez-Navarro, Arturo Schachtner, Thomas Stervbo, Ulrik Sefrin, Anett Stein, Maik Westhoff, Timm H. Reinke, Petra Klipp, Edda Babel, Nina Neumann, Avidan U. Or-Guil, Michal PLoS Comput Biol Research Article BK virus (BKV) associated nephropathy affects 1–10% of kidney transplant recipients, leading to graft failure in about 50% of cases. Immune responses against different BKV antigens have been shown to have a prognostic value for disease development. Data currently suggest that the structural antigens and regulatory antigens of BKV might each trigger a different mode of action of the immune response. To study the influence of different modes of action of the cellular immune response on BKV clearance dynamics, we have analysed the kinetics of BKV plasma load and anti-BKV T cell response (Elispot) in six patients with BKV associated nephropathy using ODE modelling. The results show that only a small number of hypotheses on the mode of action are compatible with the empirical data. The hypothesis with the highest empirical support is that structural antigens trigger blocking of virus production from infected cells, whereas regulatory antigens trigger an acceleration of death of infected cells. These differential modes of action could be important for our understanding of BKV resolution, as according to the hypothesis, only regulatory antigens would trigger a fast and continuous clearance of the viral load. Other hypotheses showed a lower degree of empirical support, but could potentially explain the clearing mechanisms of individual patients. Our results highlight the heterogeneity of the dynamics, including the delay between immune response against structural versus regulatory antigens, and its relevance for BKV clearance. Our modelling approach is the first that studies the process of BKV clearance by bringing together viral and immune kinetics and can provide a framework for personalised hypotheses generation on the interrelations between cellular immunity and viral dynamics. Public Library of Science 2018-05-10 /pmc/articles/PMC5944912/ /pubmed/29746472 http://dx.doi.org/10.1371/journal.pcbi.1005998 Text en © 2018 Blazquez-Navarro et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Blazquez-Navarro, Arturo
Schachtner, Thomas
Stervbo, Ulrik
Sefrin, Anett
Stein, Maik
Westhoff, Timm H.
Reinke, Petra
Klipp, Edda
Babel, Nina
Neumann, Avidan U.
Or-Guil, Michal
Differential T cell response against BK virus regulatory and structural antigens: A viral dynamics modelling approach
title Differential T cell response against BK virus regulatory and structural antigens: A viral dynamics modelling approach
title_full Differential T cell response against BK virus regulatory and structural antigens: A viral dynamics modelling approach
title_fullStr Differential T cell response against BK virus regulatory and structural antigens: A viral dynamics modelling approach
title_full_unstemmed Differential T cell response against BK virus regulatory and structural antigens: A viral dynamics modelling approach
title_short Differential T cell response against BK virus regulatory and structural antigens: A viral dynamics modelling approach
title_sort differential t cell response against bk virus regulatory and structural antigens: a viral dynamics modelling approach
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944912/
https://www.ncbi.nlm.nih.gov/pubmed/29746472
http://dx.doi.org/10.1371/journal.pcbi.1005998
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