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BIOMD0000000546 - Miao2010 - Innate and adaptive immune responses to primary Influenza A Virus infection

 

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Reference Publication
Publication ID: 20410284
Miao H, Hollenbaugh JA, Zand MS, Holden-Wiltse J, Mosmann TR, Perelson AS, Wu H, Topham DJ.
Quantifying the early immune response and adaptive immune response kinetics in mice infected with influenza A virus.
J. Virol. 2010 Jul; 84(13): 6687-6698
Department of Biostatistics and Computational Biology, University of Rochester, Rochester, New York 146421, USA.  [more]
Model
Original Model: Miao2010_FluImmuneResponse...
Submitter: Alain Leblanc
Submission ID: MODEL1405150000
Submission Date: 15 May 2014 19:46:39 UTC
Last Modification Date: 10 Oct 2014 12:00:17 UTC
Creation Date: 04 Sep 2014 17:07:56 UTC
Encoders:  Vijayalakshmi Chelliah
   Alain Leblanc
set #1
bqbiol:isVersionOf Gene Ontology adaptive immune response
Gene Ontology innate immune response
set #2
bqmodel:isDerivedFrom BioModels Database MODEL1406230000
set #3
bqbiol:hasTaxon Taxonomy Influenza A virus (strain A/X-31 H3N2)
Taxonomy Murinae
set #4
bqbiol:hasVersion Human Disease Ontology influenza
Notes
Miao2010 - Innate and adaptive immune responses to primary Influenza A Virus infection

This model is described in the article:

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.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Model
Publication ID: 20410284 Submission Date: 15 May 2014 19:46:39 UTC Last Modification Date: 10 Oct 2014 12:00:17 UTC Creation Date: 04 Sep 2014 17:07:56 UTC
Mathematical expressions
Reactions
re1 re3 re5 re6
re7      
Physical entities
Compartments Species Types Species
default Virus      
Infected_Cell      
Uninfected_Cell      
  Ep Eps V
s4 s5 s6
s7    
Global parameters
rho_E beta_a delta_Es pi_a
c_V      
Reactions (5)
 
 re1 [Ep] → [Eps];   {V} , {Ep} , {V} , {Ep} , {V}
 
 re3 [s4] → [Ep];   {Ep} , {Ep}
 
 re5 [Eps] → [s5];   {Eps} , {Eps}
 
 re6 [V] → [s6];   {V} , {V}
 
 re7 [s7] → [V];   {Eps} , {Eps} , {Eps}
 
  Spatial dimensions: 3.0  Compartment size: 1.0  (Units: volume)
 
 Ep
Compartment: default
Initial amount: 580000.0
 
 Eps
Compartment: default
Initial amount: 0.0
 
 V
Compartment: default
Initial amount: 1473.0
 
 s4
Compartment: default
Initial amount: 0.0
 
 s5
Compartment: default
Initial amount: 0.0
 
 s6
Compartment: default
Initial amount: 0.0
 
 s7
Compartment: default
Initial amount: 0.0
 
Global Parameters (5)
 
 rho_E
Value: 6.2E-8   (Units: substance)
Constant
 
 beta_a
Value: 2.4E-6   (Units: substance)
Constant
 
 delta_Es
Value: 0.6   (Units: substance)
Constant
 
   pi_a
Value: 100.0   (Units: substance)
Constant
 
 c_V
Value: 4.2   (Units: substance)
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000546

Curator's comment: (updated: 04 Sep 2014 13:48:48 GMT)

Parameter scan was done with varying values (1e-06 to 1)of beta_a. The green plot in figure 6A for Ep and Ep* (Eps in the model) that correspond to beta_a=1e-06 has been reproduced here.

The simulation was done using Copasi v4.12 (Build 81). The plots were generated using Gnuplot.

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