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Bulletin of Mathematical Biology

, Volume 81, Issue 12, pp 4951–4976 | Cite as

Modelling the Host Immune Response to Mature and Immature Dengue Viruses

  • Milen Borisov
  • Gabriel Dimitriu
  • Peter RashkovEmail author
Original Article

Abstract

Immature dengue virions contained in patient blood samples are essentially not infectious because the uncleaved surface protein prM renders them incompetent for membrane fusion. However, the immature virions regain full infectivity when they interact with anti-prM antibodies, and once opsonised virion fusion into Fc receptor-expressing cells is facilitated. We propose a within-host mathematical model for the immune response which takes into account the dichotomy between mature infectious and immature noninfectious dengue virions. The model accounts for experimental observations on the different interactions of plasmacytoid dendritic cells with infected cells producing virions with different infectivity. We compute the basic reproduction number as a function of the proportion of infected cells producing noninfectious virions and use numerical simulations to compare the host’s immune response in a primary and a secondary dengue infections. The results can be placed in the immunoregulatory framework with plasmacytoid dendritic cells serving as a bridge between the innate and adaptive immune response, and pose questions for potential experimental work to validate hypothesis about the evolutionary context whereby the virus strives to maximise its chance for transmission from the human host to the mosquito vector.

Keywords

Dengue Mathematical model Viral dynamics Immune response 

Mathematics Subject Classification

34A34 92B05 49Q12 

Notes

Acknowledgements

This publication is based on work from COST Action CA16227 Investigation & Mathematical Analysis of Avant-garde Disease Control via Mosquito Nano-Tech-Repellents, supported by COST (European Cooperation in Science and Technology). Weblink: www.cost.eu. Peter Rashkov would like to thank the Mathematical Biosciences Institute (funded from the National Science Foundation Division of Mathematical Sciences and supported by The Ohio State University) for the opportunity to participate in the Emphasis Semester on Infectious Diseases: Data, Modelling, Decisions (Spring 2018). The authors thank Libin Rong and Nikolay I. Nikolov for the helpful discussions during the manuscript revision.

Supplementary material

11538_2019_664_MOESM1_ESM.pdf (706 kb)
Supplementary material 1 (pdf 706 KB)

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Copyright information

© Society for Mathematical Biology 2019

Authors and Affiliations

  1. 1.Institute of Mathematics and InformaticsBulgarian Academy of SciencesSofiaBulgaria
  2. 2.University of Medicine and Pharmacy “Grigore T. Popa”, Universitatii 16IaşiRomania

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