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Modelling the Host Immune Response to Mature and Immature Dengue Viruses

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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.

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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.

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Authors and Affiliations

  1. Institute of Mathematics and Informatics, Bulgarian Academy of Sciences, 1113, Sofia, Bulgaria

    Milen Borisov & Peter Rashkov

  2. University of Medicine and Pharmacy “Grigore T. Popa”, Universitatii 16, Iaşi, Romania

    Gabriel Dimitriu

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  1. Milen Borisov
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  2. Gabriel Dimitriu
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  3. Peter Rashkov
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Correspondence to Peter Rashkov.

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Milen Borisov is partially supported by the National Scientific Program Information and Communication Technologies for a Single Digital Market in Science, Education and Security (IKTvNOS), Contract No DO1-205/23.11.2018, financed by the Ministry of Education and Science in Bulgaria. Peter Rashkov acknowledges partial support from the Bulgarian Fund for Scientific Research (FNI) under Contract DKOST01/29.

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Borisov, M., Dimitriu, G. & Rashkov, P. Modelling the Host Immune Response to Mature and Immature Dengue Viruses. Bull Math Biol 81, 4951–4976 (2019). https://doi.org/10.1007/s11538-019-00664-3

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  • DOI: https://doi.org/10.1007/s11538-019-00664-3

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