ABSTRACT:
Miao2010 - Innate and adaptive immune
responses to primary Influenza A Virus infection
This model is described in the article:
Quantifying the early immune
response and adaptive immune response kinetics in mice infected
with influenza A virus.
Miao H, Hollenbaugh JA, Zand MS,
Holden-Wiltse J, Mosmann TR, Perelson AS, Wu H, Topham DJ.
J. Virol. 2010 Jul; 84(13):
6687-6698
Abstract:
Seasonal and pandemic influenza A virus (IAV) continues to
be a public health threat. However, we lack a detailed and
quantitative understanding of the immune response kinetics to
IAV infection and which biological parameters most strongly
influence infection outcomes. To address these issues, we use
modeling approaches combined with experimental data to
quantitatively investigate the innate and adaptive immune
responses to primary IAV infection. Mathematical models were
developed to describe the dynamic interactions between target
(epithelial) cells, influenza virus, cytotoxic T lymphocytes
(CTLs), and virus-specific IgG and IgM. IAV and immune kinetic
parameters were estimated by fitting models to a large data set
obtained from primary H3N2 IAV infection of 340 mice. Prior to
a detectable virus-specific immune response (before day 5), the
estimated half-life of infected epithelial cells is
approximately 1.2 days, and the half-life of free infectious
IAV is approximately 4 h. During the adaptive immune response
(after day 5), the average half-life of infected epithelial
cells is approximately 0.5 days, and the average half-life of
free infectious virus is approximately 1.8 min. During the
adaptive phase, model fitting confirms that CD8(+) CTLs are
crucial for limiting infected cells, while virus-specific IgM
regulates free IAV levels. This may imply that CD4 T cells and
class-switched IgG antibodies are more relevant for generating
IAV-specific memory and preventing future infection via a more
rapid secondary immune response. Also, simulation studies were
performed to understand the relative contributions of
biological parameters to IAV clearance. This study provides a
basis to better understand and predict influenza virus
immunity.
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Alain Leblanc 
