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BIOMD0000000528 - Fribourg2014 - Dynamics of viral antagonism and innate immune response (H1N1 influenza A virus - Cal/09)

 

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Reference Publication
Publication ID: 24594370
Fribourg M, Hartmann B, Schmolke M, Marjanovic N, Albrecht RA, García-Sastre A, Sealfon SC, Jayaprakash C, Hayot F.
Model of influenza A virus infection: dynamics of viral antagonism and innate immune response.
J. Theor. Biol. 2014 Jun; 351: 47-57
Department of Neurology and Center for Translational Systems Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.  [more]
Model
Original Model: BIOMD0000000528.origin
Submitter: Miguel Fribourg
Submission ID: MODEL1403310002
Submission Date: 31 Mar 2014 19:14:56 UTC
Last Modification Date: 24 Feb 2015 20:30:12 UTC
Creation Date: 03 Apr 2014 13:51:13 UTC
Encoders:  Vijayalakshmi Chelliah
   Miguel Fribourg
set #1
bqmodel:isDerivedFrom PubMed 20739535
PubMed 20159146
set #2
bqbiol:hasVersion Human Disease Ontology swine influenza
set #3
bqbiol:hasProperty Mathematical Modelling Ontology MAMO_0000046
set #4
bqbiol:occursIn Cell Type Ontology dendritic cell, human
set #5
bqbiol:hasTaxon Taxonomy H1N1 swine influenza virus
Taxonomy Homo sapiens
set #6
bqbiol:isVersionOf Gene Ontology defense response, incompatible interaction
Notes
Fribourg2014 - Dynamics of viral antagonism and innate immune response (H1N1 influenza A virus - Cal/09)

The dynamics of the interplay between the viral antagonism and the innate immune response has been studied using modelling approaches. The responses of human monocyte-derived dendritic cells infected by two influenza A H1N1 strains (the pandemic swine-origin A/California/4/2009 (Cal/09) and the seasonal A/New Caledonia/20/1999 (NC/99)) that have different clinical outcomes have been modelled. From the time course gene expression measurements of a set of selected genes, the dynamic features of viral antagonism and innate immune response are extracted. It is found that the strength and the time scale of action of viral antagonism is significantly different between the two viruses. This model describes the viral infection by seasonal Cal/09.

This model is described in the article:

Fribourg M, Hartmann B, Schmolke M, Marjanovic N, Albrecht RA, García-Sastre A, Sealfon SC, Jayaprakash C, Hayot F.
J Theor Biol. 2014 Mar 2;351C:47-57.

Abstract:

Viral antagonism of host responses is an essential component of virus pathogenicity. The study of the interplay between immune response and viral antagonism is challenging due to the involvement of many processes acting at multiple time scales. Here we develop an ordinary differential equation model to investigate the early, experimentally measured, responses of human monocyte-derived dendritic cells to infection by two H1N1 influenza A viruses of different clinical outcomes: pandemic A/California/4/2009 and seasonal A/New Caledonia/20/1999. Our results reveal how the strength of virus antagonism, and the time scale over which it acts to thwart the innate immune response, differs significantly between the two viruses, as is made clear by their impact on the temporal behavior of a number of measured genes. The model thus sheds light on the mechanisms that underlie the variability of innate immune responses to different H1N1 viruses.

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: 24594370 Submission Date: 31 Mar 2014 19:14:56 UTC Last Modification Date: 24 Feb 2015 20:30:12 UTC Creation Date: 03 Apr 2014 13:51:13 UTC
Mathematical expressions
Reactions
J1 J2 J3 J4
J5 J6 J7 J8
J9 J10 J11 J12
Rules
Assignment Rule (variable: NS) Assignment Rule (variable: IC1) Assignment Rule (variable: IC2) Assignment Rule (variable: IC2ifa)
Assignment Rule (variable: TJ)      
Physical entities
Compartments Species Types Species
default mRNA      
Protein      
       
Environment mRNA      
Protein      
  IFNb_env IFNa_env TNFenv
     
Cell mRNA      
Protein      
  w IFNb_mRNA STATP2n
SOCS1m IRF7m IRF7Pn
IFNa_mRNA TNFam STATm
STAT    
Global parameters
NS r5 n3 bm
IC1 sp delta1 n1
IC2 sv delta2 n2
IC2ifa TJ TJtot K3
K9 delta r0 k15
tao1 C vmax2 NA
K2 K5 tao3 r3
k8 tao4 k11 k14
tao6 k12 k16 tao8
vmax17 K17 r1 rmax20
K20 tao9 vmax19 K19
r4 k26 tao12 k28
tao13      
Reactions (12)
 
 J1 [w] → [IFNb_mRNA];   {IRF7Pn}
 
 J2 [w] → [IFNb_env];   {IFNb_mRNA}
 
 J3 [w] → [STATP2n];   {STAT}
 
 J4 [w] → [SOCS1m];   {STATP2n}
 
 J5 [w] → [IRF7m];   {STATP2n} , {IRF7Pn}
 
 J6 [w] → [IRF7Pn];   {IRF7m}
 
 J7 [w] → [IFNa_mRNA];   {IRF7Pn}
 
 J8 [w] → [IFNa_env];   {IFNa_mRNA}
 
 J9 [w] → [TNFam];   {TNFenv}
 
 J10 [w] → [TNFenv];   {TNFam}
 
 J11 [w] → [STATm];   {STATP2n}
 
 J12 [w] → [STAT];   {STATm}
 
Rules (5)
 
 Assignment Rule (name: NS) NS = r5*time^n3/(bm^n3+time^n3)
 
 Assignment Rule (name: IC1) IC1 = (1+sp*(NS/delta1)^n1)/(1+(NS/delta1)^n1)
 
 Assignment Rule (name: IC2) IC2 = 1
 
 Assignment Rule (name: IC2ifa) IC2ifa = 1
 
 Assignment Rule (name: TJ) TJ = TJtot*(IFNb_env+IFNa_env)/(K3+IFNb_env+IFNa_env)*1/(1+K9*SOCS1m/delta)
 
  Spatial dimensions: 3.0  Compartment size: 1.0  (Units: volume)
 Environment Spatial dimensions: 3.0  Compartment size: 1.0  (Units: volume)
 
 IFNb_env
Compartment: Environment
Initial concentration: 0.0
 
 IFNa_env
Compartment: Environment
Initial concentration: 0.0
 
 TNFenv
Compartment: Environment
Initial concentration: 0.0
 
 Cell Spatial dimensions: 3.0  Compartment size: 1.0  (Units: volume)
 
 w
Compartment: Cell
Initial concentration: 0.0
 
 IFNb_mRNA
Compartment: Cell
Initial concentration: 0.0
 
 STATP2n
Compartment: Cell
Initial concentration: 0.0
 
 SOCS1m
Compartment: Cell
Initial concentration: 0.0
 
 IRF7m
Compartment: Cell
Initial concentration: 0.0
 
 IRF7Pn
Compartment: Cell
Initial concentration: 0.0
 
 IFNa_mRNA
Compartment: Cell
Initial concentration: 0.0
 
 TNFam
Compartment: Cell
Initial concentration: 0.0
 
 STATm
Compartment: Cell
Initial concentration: 0.0
 
 STAT
Compartment: Cell
Initial concentration: 0.1
 
Global Parameters (49)
 
   NS  
 
   r5
Value: 1.0   (Units: dimensionless)
Constant
 
   n3
Value: 5.0   (Units: substance)
Constant
 
   bm
Value: 6.0   (Units: substance)
Constant
 
   IC1  
 
   sp
Value: 0.3   (Units: substance)
Constant
 
   delta1
Value: 0.1   (Units: substance)
Constant
 
   n1
Value: 1.0   (Units: substance)
Constant
 
   IC2  
 
   sv
Value: 0.1   (Units: substance)
Constant
 
   delta2
Value: 0.4   (Units: substance)
Constant
 
   n2
Value: 5.0   (Units: substance)
Constant
 
   IC2ifa  
 
   TJ  
 
   TJtot
Value: 1.0E-4   (Units: substance)
Constant
 
   K3
Value: 0.0043   (Units: substance)
Constant
 
   K9
Value: 780.0   (Units: substance)
Constant
 
   delta
Value: 3.0E-4   (Units: substance)
Constant
 
   r0
Value: 0.0010   (Units: substance)
Constant
 
   k15
Value: 3.6E-8   (Units: substance)
Constant
 
   tao1
Value: 2.5   (Units: substance)
Constant
 
   C
Value: 500000.0   (Units: substance)
Constant
 
   vmax2
Value: 72000.0   (Units: substance)
Constant
 
   NA
Value: 6.023E23   (Units: substance)
Constant
 
   K2
Value: 0.0020   (Units: substance)
Constant
 
   K5
Value: 0.01   (Units: substance)
Constant
 
   tao3
Value: 0.56   (Units: substance)
Constant
 
   r3
Value: 1.0E-7   (Units: substance)
Constant
 
   k8
Value: 0.0036   (Units: substance)
Constant
 
   tao4
Value: 0.46   (Units: substance)
Constant
 
   k11
Value: 3.6E-4   (Units: substance)
Constant
 
   k14
Value: 3.204E-7   (Units: substance)
Constant
 
   tao6
Value: 1.0
Constant
 
   k12
Value: 360.0   (Units: substance)
Constant
 
   k16
Value: 0.36   (Units: substance)
Constant
 
   tao8
Value: 2.0   (Units: substance)
Constant
 
   vmax17
Value: 72000.0   (Units: substance)
Constant
 
   K17
Value: 0.0020   (Units: substance)
Constant
 
   r1
Value: 1.0E-4   (Units: substance)
Constant
 
   rmax20
Value: 0.0010   (Units: substance)
Constant
 
   K20
Value: 6.0E-4   (Units: substance)
Constant
 
   tao9
Value: 2.0   (Units: substance)
Constant
 
   vmax19
Value: 154800.0   (Units: substance)
Constant
 
   K19
Value: 0.0040   (Units: substance)
Constant
 
   r4
Value: 1.0E-5   (Units: substance)
Constant
 
   k26
Value: 0.360085   (Units: substance)
Constant
 
   tao12
Value: 1.0   (Units: substance)
Constant
 
   k28
Value: 360.0   (Units: substance)
Constant
 
   tao13
Value: 15.0   (Units: substance)
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000528

Curator's comment: (updated: 03 Apr 2014 14:50:18 BST)

Figure 5A of the reference publication has been reproduced. The simulation was done using SBML odeSolver and the plot was generated using Gnuplot.

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