Towards a quantitative understanding of the within-host dynamics of influenza A infections

Abstract

Although the influenza A virus has been extensively studied, a quantitative understanding of the infection dynamics is still lacking. To make progress in this direction, we designed several mathematical models and compared them with data from influenza A infections of mice. We find that the immune response (IR) plays an important part in the infection dynamics. Both an innate and an adaptive IR are required to provide adequate explanation of the data. In contrast, regrowth of epithelial cells did not seem to be an important mechanism on the time scale of the infection. We also find that different model variants for both innate and adaptive responses fit the data well, indicating the need for additional data to allow further model discrimination.

Time and dose-dependent risk of pneumococcal pneumonia following influenza: a model for within-host interaction between influenza andStreptococcus pneumoniae

“…We proceed by first presenting mathematical models previously proposed to describe the within-host dynamics of influenza [28] and pneumococcal [29] infections in isolation. Each model attempts to capture the kinetics of pathogen proliferation, the resultant immune response and its impact on pathogen load during the course of an infection.…”

“…The mathematical equations describing the system and the parameter estimates are presented in the electronic supplementary material, equations S1 and table S1, respectively. Handel et al [28] parametrized the within-host influenza model by statistical fitting to data from two separate experimental studies: (i) the study by Kris et al [33], which observed viral loads in both wild-type (normal) and nude, athymic (no antibody response) mice during an H3N2 infection, and (ii) the study by Iwasaki & Nozima [34], which documented viral loads, IFN and antibody levels, as well as lung lesions in mice with H1N1 infection under various permutations of treatments. We illustrate representative viral titres and different measures of immune response over the course of the infection, as predicted by the model, in the electronic supplementary material, figures S1 and S2.…”

“…The model we examine here is adapted from that proposed by Handel et al [28]. Following infection, the virus proliferates via infection of 'target cells', which then generate more viral particles.…”

“…Schematic diagram of the within-host kinetics and the immunemediated interaction. Schematic diagrams for within models for influenza infection (in blue) [28] and pneumococcal pneumonia infection (in red) [29]. The virus (V) targets epithelial cells (E U ), which become infected (E I ) after some latency (E E ).…”

“…Both the influenza [28] and pneumococcal pneumonia [29] models were developed as stand-alone models, parametrized with data from experimental challenge with the focal pathogen. We then coupled these models on the basis of one of the proposed mechanisms of viral-bacterial interaction, whereby cytokines expressed as a response to viral infection interfere with the functioning of macrophage-based response to subsequent bacterial exposure [22,25].…”