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Assessing mathematical models of influenza infections using features of the immune response.

Dobrovolny HM, Reddy MB, Kamal MA, Rayner CR, Beauchemin CA - PLoS ONE (2013)

Bottom Line: Despite the lack of sufficiently diverse experimental data describing the time course of the various immune response components, published mathematical models were constructed from limited human or animal data using various strategies and simplifying assumptions.We test these existing models by confronting them with experimental data and find that no single model agrees completely with the variety of influenza viral kinetics responses observed experimentally when various immune response components are suppressed.Our analysis highlights the strong and weak points of each mathematical model and highlights areas where additional experimental data could elucidate specific mechanisms, constrain model design, and complete our understanding of the immune response to influenza.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics and Astronomy, Texas Christian University, Fort Worth, Texas, USA.

ABSTRACT
The role of the host immune response in determining the severity and duration of an influenza infection is still unclear. In order to identify severity factors and more accurately predict the course of an influenza infection within a human host, an understanding of the impact of host factors on the infection process is required. Despite the lack of sufficiently diverse experimental data describing the time course of the various immune response components, published mathematical models were constructed from limited human or animal data using various strategies and simplifying assumptions. To assess the validity of these models, we assemble previously published experimental data of the dynamics and role of cytotoxic T lymphocytes, antibodies, and interferon and determined qualitative key features of their effect that should be captured by mathematical models. We test these existing models by confronting them with experimental data and find that no single model agrees completely with the variety of influenza viral kinetics responses observed experimentally when various immune response components are suppressed. Our analysis highlights the strong and weak points of each mathematical model and highlights areas where additional experimental data could elucidate specific mechanisms, constrain model design, and complete our understanding of the immune response to influenza.

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Mathematical models of the adaptive (top) and innate (bottom) immune responses to influenza.The adaptive immune response typically includes Abs and CTLs. The generation of Abs and CTLs are represented with different simplifying assumptions, so the actual processes are not depicted here. All models reviewed here assume that Abs bind to and remove virus while CTLs cause the death of infectious cells. The innate immune response is represented by IFN. Since IFN has many antiviral effects in vivo, models have different implementations of IFN's effect. Details of individual models are discussed in the text and in Supplement S2.
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pone-0057088-g003: Mathematical models of the adaptive (top) and innate (bottom) immune responses to influenza.The adaptive immune response typically includes Abs and CTLs. The generation of Abs and CTLs are represented with different simplifying assumptions, so the actual processes are not depicted here. All models reviewed here assume that Abs bind to and remove virus while CTLs cause the death of infectious cells. The innate immune response is represented by IFN. Since IFN has many antiviral effects in vivo, models have different implementations of IFN's effect. Details of individual models are discussed in the text and in Supplement S2.

Mentions: Here, we review eight previously published models of within host influenza infections that explicitly incorporate at least one of the following immune responses: Abs, CTLs, and IFN [2], [4], [6], [22], [23], [31], [32]. We limited our investigation to models with parameters determined from experimental data. A summary of the number of variables, parameters, and immune components incorporated in each model is presented in Table 2, with details provided in supplemental material S2. General schematics of the models' implementation of the adaptive immune response (Abs and CTLs) and the innate immune response (IFN) are shown in Fig. 3. In the case of the Miao et al. model [23], we re-fit their model to their data using an alternative approach and distinguish these two fits of the same model as Miao split (our fit) and Miao full (published). See the Methods section for details.


Assessing mathematical models of influenza infections using features of the immune response.

Dobrovolny HM, Reddy MB, Kamal MA, Rayner CR, Beauchemin CA - PLoS ONE (2013)

Mathematical models of the adaptive (top) and innate (bottom) immune responses to influenza.The adaptive immune response typically includes Abs and CTLs. The generation of Abs and CTLs are represented with different simplifying assumptions, so the actual processes are not depicted here. All models reviewed here assume that Abs bind to and remove virus while CTLs cause the death of infectious cells. The innate immune response is represented by IFN. Since IFN has many antiviral effects in vivo, models have different implementations of IFN's effect. Details of individual models are discussed in the text and in Supplement S2.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585335&req=5

pone-0057088-g003: Mathematical models of the adaptive (top) and innate (bottom) immune responses to influenza.The adaptive immune response typically includes Abs and CTLs. The generation of Abs and CTLs are represented with different simplifying assumptions, so the actual processes are not depicted here. All models reviewed here assume that Abs bind to and remove virus while CTLs cause the death of infectious cells. The innate immune response is represented by IFN. Since IFN has many antiviral effects in vivo, models have different implementations of IFN's effect. Details of individual models are discussed in the text and in Supplement S2.
Mentions: Here, we review eight previously published models of within host influenza infections that explicitly incorporate at least one of the following immune responses: Abs, CTLs, and IFN [2], [4], [6], [22], [23], [31], [32]. We limited our investigation to models with parameters determined from experimental data. A summary of the number of variables, parameters, and immune components incorporated in each model is presented in Table 2, with details provided in supplemental material S2. General schematics of the models' implementation of the adaptive immune response (Abs and CTLs) and the innate immune response (IFN) are shown in Fig. 3. In the case of the Miao et al. model [23], we re-fit their model to their data using an alternative approach and distinguish these two fits of the same model as Miao split (our fit) and Miao full (published). See the Methods section for details.

Bottom Line: Despite the lack of sufficiently diverse experimental data describing the time course of the various immune response components, published mathematical models were constructed from limited human or animal data using various strategies and simplifying assumptions.We test these existing models by confronting them with experimental data and find that no single model agrees completely with the variety of influenza viral kinetics responses observed experimentally when various immune response components are suppressed.Our analysis highlights the strong and weak points of each mathematical model and highlights areas where additional experimental data could elucidate specific mechanisms, constrain model design, and complete our understanding of the immune response to influenza.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics and Astronomy, Texas Christian University, Fort Worth, Texas, USA.

ABSTRACT
The role of the host immune response in determining the severity and duration of an influenza infection is still unclear. In order to identify severity factors and more accurately predict the course of an influenza infection within a human host, an understanding of the impact of host factors on the infection process is required. Despite the lack of sufficiently diverse experimental data describing the time course of the various immune response components, published mathematical models were constructed from limited human or animal data using various strategies and simplifying assumptions. To assess the validity of these models, we assemble previously published experimental data of the dynamics and role of cytotoxic T lymphocytes, antibodies, and interferon and determined qualitative key features of their effect that should be captured by mathematical models. We test these existing models by confronting them with experimental data and find that no single model agrees completely with the variety of influenza viral kinetics responses observed experimentally when various immune response components are suppressed. Our analysis highlights the strong and weak points of each mathematical model and highlights areas where additional experimental data could elucidate specific mechanisms, constrain model design, and complete our understanding of the immune response to influenza.

Show MeSH
Related in: MedlinePlus