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fribourg2

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fribourg2

The SBML for this model was obtained from the BioModels database (BioModels ID: BIOMD0000000529) Biomodels notes: Figure 5B of the reference publication has been reproduced. The simulation was done using SBML odeSolver and the plot was generated using Gnuplot. JWS Online curation: This model was curated by reproducing the figures as described in the BioModels Notes. No additional changes were made.

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Manuscript information

Model of influenza A virus infection: dynamics of viral antagonism and innate immune response.

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

Unit definitions 6

Unit definitions have no effect on the numerical analysis of the model. It remains the responsibility of the modeler to ensure the internal numerical consistency of the model. If units are provided, however, the consistency of the model units will be checked.

Name Definition
— 1e-06 mole
— 1.0 litre
— 1.0 metre^(2.0)
— 1.0 metre
— 3600.0 second
— 1.0 dimensionless

Compartments 3

Id Name Spatial dimensions Size
c2 Environment 3.0 1.0 volume
compartment Cell 3.0 1.0 volume
default — 3.0 1.0 volume

Species 13

Id Name Initial quantity Compartment Fixed
IFNa_env IFNa_env 0.0 <substance_units>/volume c2 (Environment) ✘
IFNa_mRNA IFNa_mRNA 0.0 <substance_units>/volume compartment (Cell) ✘
IFNb_env IFNb_env 0.0 <substance_units>/volume c2 (Environment) ✘
IFNb_mRNA IFNb_mRNA 0.0 <substance_units>/volume compartment (Cell) ✘
IRF7Pn IRF7Pn 0.0 <substance_units>/volume compartment (Cell) ✘
IRF7m IRF7m 0.0 <substance_units>/volume compartment (Cell) ✘
SOCS1m SOCS1m 0.0 <substance_units>/volume compartment (Cell) ✘
STAT STAT 0.1 <substance_units>/volume compartment (Cell) ✘
STATP2n STATP2n 0.0 <substance_units>/volume compartment (Cell) ✘
STATm STATm 0.0 <substance_units>/volume compartment (Cell) ✘
TNFam TNFam 0.0 <substance_units>/volume compartment (Cell) ✘
TNFenv TNFenv 0.0 <substance_units>/volume c2 (Environment) ✘
w w 0.0 <substance_units>/volume compartment (Cell) ✔

Initial assignments 0

Initial assignments are expressions that are evaluated at time=0. It is not recommended to create initial assignments for all model entities. Restrict the use of initial assignments to cases where a value is expressed in terms of values or sizes of other model entities. Note that it is not permitted to have both an initial assignment and an assignment rule for a single model entity.

Definition
Reactions 12
Id Name Objective coefficient Reaction Equation and Kinetic Law Flux bounds
J1 J1 w > IFNb_mRNA

(r0 * IC1 + k15 * IRF7Pn) * IC2 - IFNb_mRNA * log(2) / tao1
J10 J10 w > TNFenv

1000000000 * C * vmax19 / NA * TNFam / (K19 + TNFam)
J11 J11 w > STATm

(r4 * IC1 + k26 * STATP2n) * IC2 - STATm * log(2) / tao12
J12 J12 w > STAT

k28 * STATm - STAT * log(2) / tao13
J2 J2 w > IFNb_env

1000000000 * C * vmax2 / NA * IFNb_mRNA / (K2 + IFNb_mRNA)
J3 J3 w > STATP2n

K5 * TJ * STAT / 2 / (K5 + STAT) - STATP2n * log(2) / tao3
J4 J4 w > SOCS1m

(r3 * IC1 + k8 * STATP2n) * IC2 - SOCS1m * log(2) / tao4
J5 J5 w > IRF7m

(k11 * STATP2n + k14 * IRF7Pn) * IC2 - IRF7m * log(2) / tao6
J6 J6 w > IRF7Pn

k12 * IC1 * IRF7m
J7 J7 w > IFNa_mRNA

k16 * IRF7Pn * IC2ifa - IFNa_mRNA * log(2) / tao8
J8 J8 w > IFNa_env

1000000000 * C * vmax17 / NA * IFNa_mRNA / (K17 + IFNa_mRNA)
J9 J9 w > TNFam

(r1 * IC1 + rmax20 * TNFenv / (K20 + TNFenv)) * IC2 - TNFam * log(2) / tao9

Parameters 0   49

Global parameters

Id Value
C 500000.0 substance
IC1 0.0
IC2 0.0
IC2ifa 0.0
K17 0.002 substance
K19 0.004 substance
K2 72000.0 substance
K20 0.0006 substance
K3 0.0043 substance
K5 0.01 substance
K9 780.0 substance
NA 6.023e+23 substance
NS 0.0
TJ 0.0
TJtot 0.0001 substance
bm 4.5 substance
delta 0.0003 substance
delta1 0.1 substance
delta2 0.4 substance
k11 0.00036 substance
k12 3600.0 substance
k14 3.204e-07 substance
k15 3.6e-05 substance
k16 3600.0 substance
k26 0.360085 substance
k28 360.0 substance
k8 0.0036 substance
n1 5.0 substance
n2 5.0 substance
n3 8.0 substance
r0 0.003 substance
r1 0.00025 substance
r3 1e-07 substance
r4 1e-06 substance
r5 1.0 dimensionless
rmax20 0.001 substance
sp 0.1 substance
sv 0.1 substance
tao1 2.5 substance
tao12 1.0 substance
tao13 15.0 substance
tao3 0.56 substance
tao4 0.46 substance
tao6 1.0
tao8 2.0 substance
tao9 2.0 substance
vmax17 72000.0 substance
vmax19 154800.0 substance
vmax2 72000.0 substance

Local parameters

Id Value Reaction

Rules 0   0   5

Assignment rules

Definition
NS = r5 * pow(time, n3) / (pow(bm, n3) + pow(time, n3))
IC1 = (1.0 + sp * pow(NS / delta1, n1)) / (1.0 + pow(NS / delta1, n1))
IC2 = (1.0 + sv * pow(NS / delta2, n2)) / (1.0 + pow(NS / delta2, n2))
TJ = TJtot * (IFNb_env + IFNa_env) / (K3 + IFNb_env + IFNa_env) * 1.0 / (1.0 + K9 * SOCS1m / delta)
IC2ifa = (1.0 + 3.0 * sv * pow(NS / delta2, n2)) / (1.0 + pow(NS / delta2, n2))

Rate rules

Definition

Algebraic rules

Definition

Events 0

Trigger Assignments