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

Arturo Blazquez-Navarro, Thomas Schachtner, Ulrik Stervbo, Anett Sefrin, Maik Stein, Timm H. Westhoff, Petra Reinke, Edda Klipp, Nina Babel, Avidan U. Neumann, Michal Or-Guil

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere1005998
JournalPLoS Computational Biology
Volume14
Issue number5
DOIs
StatePublished - May 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018 Blazquez-Navarro et al. http://creativecommons.org/licenses/by/4.0/

Funding

This work was supported by the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (01ZX1312A, D, F, G), https://www.bmbf.de/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

FundersFunder number
Bundesministerium für Bildung und Forschung01ZX1312A

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