Quantification of type i interferon inhibition by viral proteins: Ebola virus as a case study

Macauley Locke, Grant Lythe, Martín López-García, César Muñoz-Fontela, Miles Carroll, Carmen Molina-París*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Type I interferons (IFNs) are cytokines with both antiviral properties and protective roles in innate immune responses to viral infection. They induce an antiviral cellular state and link innate and adaptive immune responses. Yet, viruses have evolved different strategies to inhibit such host responses. One of them is the existence of viral proteins which subvert type I IFN responses to allow quick and successful viral replication, thus, sustaining the infection within a host. We propose mathematical models to characterise the intra-cellular mechanisms involved in viral protein antagonism of type I IFN responses, and compare three different molecular inhibition strategies. We study the Ebola viral protein, VP35, with this mathematical approach. Approximate Bayesian computation sequential Monte Carlo, together with experimental data and the mathematical models proposed, are used to perform model calibration, as well as model selection of the different hypotheses considered. Finally, we assess if model parameters are identifiable and discuss how such identifiability can be improved with new experimental data.

Original languageEnglish
Article number2441
JournalViruses
Volume13
Issue number12
DOIs
Publication statusPublished - Dec 2021
Externally publishedYes

Bibliographical note

Funding Information:
This research was funded by an EPSRC NPIF DTP studentship with support from Public Health England (awarded to M.L.). This project was partially funded by the Laboratory Directed Research and Development Program at Los Alamos National Laboratory though grant number 20210957ER (C.M.-P.).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Antagonist protein
  • Ebola
  • Immune response inhibition
  • Mathematical model
  • Type I interferon
  • Virus

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