Giuseppe
Emeritus
[Source: US National Library of Medicine, (LINK). Edited.]
J Virol. 2010 Apr 21. [Epub ahead of print]
Quantifying the Early Immune Response and Adaptive Immune Response Kinetics in Mice Infected by Influenza A Virus.
Miao H, Hollenbaugh JA, Zand MS, Holden-Wiltse J, Mosmann TR, Perelson AS, Wu H, Topham DJ. - Department of Biostatistics and Computational Biology, University of Rochester, NY, 14642; David H. Smith Center for Vaccine Biology & Immunology, Department of Microbiology and Immunology, University of Rochester, NY, 14642; Department of Medicine, Division of Nephrology, University of Rochester, NY, 14642; Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, 87545.
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 (CTL), and virus-specific IgG and IgM. IAV and immune kinetic parameters were estimated by fitting models to a large dataset obtained from primary H3N2 IAV infection of 340 mice. Prior to a detectable virus-specific immune response (< day 5), the estimated half-life of infected epithelial cells is approximately 1.2 day, and the half-life of free infectious IAV is approximately 4 hours. During the adaptive immune response (>day 5), the average half-life of infected epithelial cells is approximately 0.5 day, and the average half-life of free infectious virus is approximately 1.8 minutes. During the adaptive phase, model fitting confirms that CD8+ CTL 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 immunity.
PMID: 20410284 [PubMed - as supplied by publisher]
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J Virol. 2010 Apr 21. [Epub ahead of print]
Quantifying the Early Immune Response and Adaptive Immune Response Kinetics in Mice Infected by Influenza A Virus.
Miao H, Hollenbaugh JA, Zand MS, Holden-Wiltse J, Mosmann TR, Perelson AS, Wu H, Topham DJ. - Department of Biostatistics and Computational Biology, University of Rochester, NY, 14642; David H. Smith Center for Vaccine Biology & Immunology, Department of Microbiology and Immunology, University of Rochester, NY, 14642; Department of Medicine, Division of Nephrology, University of Rochester, NY, 14642; Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, 87545.
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 (CTL), and virus-specific IgG and IgM. IAV and immune kinetic parameters were estimated by fitting models to a large dataset obtained from primary H3N2 IAV infection of 340 mice. Prior to a detectable virus-specific immune response (< day 5), the estimated half-life of infected epithelial cells is approximately 1.2 day, and the half-life of free infectious IAV is approximately 4 hours. During the adaptive immune response (>day 5), the average half-life of infected epithelial cells is approximately 0.5 day, and the average half-life of free infectious virus is approximately 1.8 minutes. During the adaptive phase, model fitting confirms that CD8+ CTL 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 immunity.
PMID: 20410284 [PubMed - as supplied by publisher]
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