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Understanding Experimental LCMV Infection of Mice: The Role of Mathematical Models.

Bocharov G, Argilaguet J, Meyerhans A - J Immunol Res (2015)

Bottom Line: The model formulations should be tightly linked to a fundamental step called "coordinatization" (Hermann Weyl), that is, the definition of observables, parameters, and structures that enable the link with a biological phenotype.We show how the modelling approaches can be implemented to address diverse aspects of immune system functioning under normal conditions and in response to LCMV and, importantly, make quantitative predictions of the outcomes of immune system perturbations.This may highlight the notion that data-driven applications of meaningful mathematical models in infection biology remain a challenge.

View Article: PubMed Central - PubMed

Affiliation: Institute of Numerical Mathematics, Russian Academy of Sciences, Gubkina Street 8, Moscow 119333, Russia.

ABSTRACT
Virus infections represent complex biological systems governed by multiple-level regulatory processes of virus replication and host immune responses. Understanding of the infection means an ability to predict the systems behaviour under various conditions. Such predictions can only rely upon quantitative mathematical models. The model formulations should be tightly linked to a fundamental step called "coordinatization" (Hermann Weyl), that is, the definition of observables, parameters, and structures that enable the link with a biological phenotype. In this review, we analyse the mathematical modelling approaches to LCMV infection in mice that resulted in quantification of some fundamental parameters of the CTL-mediated virus control including the rates of T cell turnover, infected target cell elimination, and precursor frequencies. We show how the modelling approaches can be implemented to address diverse aspects of immune system functioning under normal conditions and in response to LCMV and, importantly, make quantitative predictions of the outcomes of immune system perturbations. This may highlight the notion that data-driven applications of meaningful mathematical models in infection biology remain a challenge.

No MeSH data available.


Related in: MedlinePlus

(a) Schematic view of acute and chronic LCMV infections including virus and cytotoxic T lymphocyte (CTL) dynamics. (b) Representation of the CTL-induced immunopathology dependence on the initial viral infectious dose at day 13 after infection (adapted from Cornberg et al. [62]). LD: low-dose infection; MD: medium-dose infection; HD: high-dose infection.
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fig1: (a) Schematic view of acute and chronic LCMV infections including virus and cytotoxic T lymphocyte (CTL) dynamics. (b) Representation of the CTL-induced immunopathology dependence on the initial viral infectious dose at day 13 after infection (adapted from Cornberg et al. [62]). LD: low-dose infection; MD: medium-dose infection; HD: high-dose infection.

Mentions: One of the best-studied model systems of viral infections is that of the lymphocytic choriomeningitis virus (LCMV) in mice (Figure 1) [1–3]. LCMV is an RNA virus of Arenaviridae that is noncytopathic in vivo. Thus, the virus itself does not cause direct damage to cells and tissues. This feature enables relating any damage that appears in the course of an infection to host responses against the virus. Another important feature of the LCMV model system is the existence of several well-characterized viral strains that differ in their replicative capacity, host range (cell tropism and mouse strain), and experimental routes of infection (intracranial versus intraperitoneal (i.p.) or intravenous (i.v.)) and thus show different infection outcomes. This enables directly linking easily measurable viral dynamic properties to pathogenic consequences and studying the fundamental issue of chronic infections.


Understanding Experimental LCMV Infection of Mice: The Role of Mathematical Models.

Bocharov G, Argilaguet J, Meyerhans A - J Immunol Res (2015)

(a) Schematic view of acute and chronic LCMV infections including virus and cytotoxic T lymphocyte (CTL) dynamics. (b) Representation of the CTL-induced immunopathology dependence on the initial viral infectious dose at day 13 after infection (adapted from Cornberg et al. [62]). LD: low-dose infection; MD: medium-dose infection; HD: high-dose infection.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4631900&req=5

fig1: (a) Schematic view of acute and chronic LCMV infections including virus and cytotoxic T lymphocyte (CTL) dynamics. (b) Representation of the CTL-induced immunopathology dependence on the initial viral infectious dose at day 13 after infection (adapted from Cornberg et al. [62]). LD: low-dose infection; MD: medium-dose infection; HD: high-dose infection.
Mentions: One of the best-studied model systems of viral infections is that of the lymphocytic choriomeningitis virus (LCMV) in mice (Figure 1) [1–3]. LCMV is an RNA virus of Arenaviridae that is noncytopathic in vivo. Thus, the virus itself does not cause direct damage to cells and tissues. This feature enables relating any damage that appears in the course of an infection to host responses against the virus. Another important feature of the LCMV model system is the existence of several well-characterized viral strains that differ in their replicative capacity, host range (cell tropism and mouse strain), and experimental routes of infection (intracranial versus intraperitoneal (i.p.) or intravenous (i.v.)) and thus show different infection outcomes. This enables directly linking easily measurable viral dynamic properties to pathogenic consequences and studying the fundamental issue of chronic infections.

Bottom Line: The model formulations should be tightly linked to a fundamental step called "coordinatization" (Hermann Weyl), that is, the definition of observables, parameters, and structures that enable the link with a biological phenotype.We show how the modelling approaches can be implemented to address diverse aspects of immune system functioning under normal conditions and in response to LCMV and, importantly, make quantitative predictions of the outcomes of immune system perturbations.This may highlight the notion that data-driven applications of meaningful mathematical models in infection biology remain a challenge.

View Article: PubMed Central - PubMed

Affiliation: Institute of Numerical Mathematics, Russian Academy of Sciences, Gubkina Street 8, Moscow 119333, Russia.

ABSTRACT
Virus infections represent complex biological systems governed by multiple-level regulatory processes of virus replication and host immune responses. Understanding of the infection means an ability to predict the systems behaviour under various conditions. Such predictions can only rely upon quantitative mathematical models. The model formulations should be tightly linked to a fundamental step called "coordinatization" (Hermann Weyl), that is, the definition of observables, parameters, and structures that enable the link with a biological phenotype. In this review, we analyse the mathematical modelling approaches to LCMV infection in mice that resulted in quantification of some fundamental parameters of the CTL-mediated virus control including the rates of T cell turnover, infected target cell elimination, and precursor frequencies. We show how the modelling approaches can be implemented to address diverse aspects of immune system functioning under normal conditions and in response to LCMV and, importantly, make quantitative predictions of the outcomes of immune system perturbations. This may highlight the notion that data-driven applications of meaningful mathematical models in infection biology remain a challenge.

No MeSH data available.


Related in: MedlinePlus