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Exploring cell tropism as a possible contributor to influenza infection severity.

Dobrovolny HM, Baron MJ, Gieschke R, Davies BE, Jumbe NL, Beauchemin CA - PLoS ONE (2010)

Bottom Line: Several mechanisms have been proposed to account for the marked increase in severity of human infections with avian compared to human influenza strains, including increased cytokine expression, poor immune response, and differences in target cell receptor affinity.Here, the potential effect of target cell tropism on disease severity is studied using a mathematical model for in-host influenza viral infection in a cell population consisting of two different cell types.This finding suggests that differences in cell tropism between influenza strains could be sufficient to cause significant differences in viral titer profiles, similar to those observed in infections with certain strains of influenza A virus.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics, Ryerson University, Toronto, Ontario, Canada.

ABSTRACT
Several mechanisms have been proposed to account for the marked increase in severity of human infections with avian compared to human influenza strains, including increased cytokine expression, poor immune response, and differences in target cell receptor affinity. Here, the potential effect of target cell tropism on disease severity is studied using a mathematical model for in-host influenza viral infection in a cell population consisting of two different cell types. The two cell types differ only in their susceptibility to infection and rate of virus production. We show the existence of a parameter regime which is characterized by high viral loads sustained long after the onset of infection. This finding suggests that differences in cell tropism between influenza strains could be sufficient to cause significant differences in viral titer profiles, similar to those observed in infections with certain strains of influenza A virus. The two target cell mathematical model offers good agreement with experimental data from severe influenza infections, as does the usual, single target cell model albeit with biologically unrealistic parameters. Both models predict that while neuraminidase inhibitors and adamantanes are only effective when administered early to treat an uncomplicated seasonal infection, they can be effective against more severe influenza infections even when administered late.

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Related in: MedlinePlus

Time of viral titer peak for different properties of the secondary cell type.The effect of varying the secondary cells' susceptibility to infection () and their rate of virus production () relative to that of the default cell type is illustrated (top) for a population of cells with an equal abundance of default and secondary cells (). Time of viral titer peak is given in days post-infection (see legend to the right of graph). The three stars indicate the specific parameter values used in the three graphs (bottom) from left to right (a to c). The graphs depict the viral titer (black), and the relative abundance of target cells of the default (blue, dashed) and secondary (blue, solid) type over the course of an in-host influenza infection when the secondary target cells' susceptibility to infection is 500-fold less, and their virus production rate is (a) 10-, (b) 100-, and (c) 1,000-fold higher than that for cells of the default type. All other parameter values are given in Table 1.
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pone-0013811-g001: Time of viral titer peak for different properties of the secondary cell type.The effect of varying the secondary cells' susceptibility to infection () and their rate of virus production () relative to that of the default cell type is illustrated (top) for a population of cells with an equal abundance of default and secondary cells (). Time of viral titer peak is given in days post-infection (see legend to the right of graph). The three stars indicate the specific parameter values used in the three graphs (bottom) from left to right (a to c). The graphs depict the viral titer (black), and the relative abundance of target cells of the default (blue, dashed) and secondary (blue, solid) type over the course of an in-host influenza infection when the secondary target cells' susceptibility to infection is 500-fold less, and their virus production rate is (a) 10-, (b) 100-, and (c) 1,000-fold higher than that for cells of the default type. All other parameter values are given in Table 1.

Mentions: Figure 1 illustrates how the time post-infection at which viral titer peaks depends on the fold difference in susceptibility to infection () and viral production rate () of the secondary cell type compared to that of the default cell type. Here we present only the case where default and secondary target cells are present in equal numbers (). Varying the fraction of target cells of the secondary type results in similar behaviour, except in the case of a nearly homogeneous cell population composed mainly of cells of the secondary type ().


Exploring cell tropism as a possible contributor to influenza infection severity.

Dobrovolny HM, Baron MJ, Gieschke R, Davies BE, Jumbe NL, Beauchemin CA - PLoS ONE (2010)

Time of viral titer peak for different properties of the secondary cell type.The effect of varying the secondary cells' susceptibility to infection () and their rate of virus production () relative to that of the default cell type is illustrated (top) for a population of cells with an equal abundance of default and secondary cells (). Time of viral titer peak is given in days post-infection (see legend to the right of graph). The three stars indicate the specific parameter values used in the three graphs (bottom) from left to right (a to c). The graphs depict the viral titer (black), and the relative abundance of target cells of the default (blue, dashed) and secondary (blue, solid) type over the course of an in-host influenza infection when the secondary target cells' susceptibility to infection is 500-fold less, and their virus production rate is (a) 10-, (b) 100-, and (c) 1,000-fold higher than that for cells of the default type. All other parameter values are given in Table 1.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2990709&req=5

pone-0013811-g001: Time of viral titer peak for different properties of the secondary cell type.The effect of varying the secondary cells' susceptibility to infection () and their rate of virus production () relative to that of the default cell type is illustrated (top) for a population of cells with an equal abundance of default and secondary cells (). Time of viral titer peak is given in days post-infection (see legend to the right of graph). The three stars indicate the specific parameter values used in the three graphs (bottom) from left to right (a to c). The graphs depict the viral titer (black), and the relative abundance of target cells of the default (blue, dashed) and secondary (blue, solid) type over the course of an in-host influenza infection when the secondary target cells' susceptibility to infection is 500-fold less, and their virus production rate is (a) 10-, (b) 100-, and (c) 1,000-fold higher than that for cells of the default type. All other parameter values are given in Table 1.
Mentions: Figure 1 illustrates how the time post-infection at which viral titer peaks depends on the fold difference in susceptibility to infection () and viral production rate () of the secondary cell type compared to that of the default cell type. Here we present only the case where default and secondary target cells are present in equal numbers (). Varying the fraction of target cells of the secondary type results in similar behaviour, except in the case of a nearly homogeneous cell population composed mainly of cells of the secondary type ().

Bottom Line: Several mechanisms have been proposed to account for the marked increase in severity of human infections with avian compared to human influenza strains, including increased cytokine expression, poor immune response, and differences in target cell receptor affinity.Here, the potential effect of target cell tropism on disease severity is studied using a mathematical model for in-host influenza viral infection in a cell population consisting of two different cell types.This finding suggests that differences in cell tropism between influenza strains could be sufficient to cause significant differences in viral titer profiles, similar to those observed in infections with certain strains of influenza A virus.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics, Ryerson University, Toronto, Ontario, Canada.

ABSTRACT
Several mechanisms have been proposed to account for the marked increase in severity of human infections with avian compared to human influenza strains, including increased cytokine expression, poor immune response, and differences in target cell receptor affinity. Here, the potential effect of target cell tropism on disease severity is studied using a mathematical model for in-host influenza viral infection in a cell population consisting of two different cell types. The two cell types differ only in their susceptibility to infection and rate of virus production. We show the existence of a parameter regime which is characterized by high viral loads sustained long after the onset of infection. This finding suggests that differences in cell tropism between influenza strains could be sufficient to cause significant differences in viral titer profiles, similar to those observed in infections with certain strains of influenza A virus. The two target cell mathematical model offers good agreement with experimental data from severe influenza infections, as does the usual, single target cell model albeit with biologically unrealistic parameters. Both models predict that while neuraminidase inhibitors and adamantanes are only effective when administered early to treat an uncomplicated seasonal infection, they can be effective against more severe influenza infections even when administered late.

Show MeSH
Related in: MedlinePlus