Perelson1993 - HIVinfection_CD4Tcells_ModelA

This a model from the article:
Dynamics of HIV infection of CD4+ T cells.
Perelson AS, Kirschner DE, De Boer R. Math Biosci
1993 Mar;114(1):81-125 8096155
,
Abstract:
We examine a model for the interaction of HIV with CD4+ T cells that considers
four populations: uninfected T cells, latently infected T cells, actively
infected T cells, and free virus. Using this model we show that many of the
puzzling quantitative features of HIV infection can be explained simply. We also
consider effects of AZT on viral growth and T-cell population dynamics. The
model exhibits two steady states, an uninfected state in which no virus is
present and an endemically infected state, in which virus and infected T cells
are present. We show that if N, the number of infectious virions produced per
actively infected T cell, is less a critical value, Ncrit, then the uninfected
state is the only steady state in the nonnegative orthant, and this state is
stable. For N > Ncrit, the uninfected state is unstable, and the endemically
infected state can be either stable, or unstable and surrounded by a stable
limit cycle. Using numerical bifurcation techniques we map out the parameter
regimes of these various behaviors. oscillatory behavior seems to lie outside
the region of biologically realistic parameter values. When the endemically
infected state is stable, it is characterized by a reduced number of T cells
compared with the uninfected state. Thus T-cell depletion occurs through the
establishment of a new steady state. The dynamics of the establishment of this
new steady state are examined both numerically and via the quasi-steady-state
approximation. We develop approximations for the dynamics at early times in
which the free virus rapidly binds to T cells, during an intermediate time scale
in which the virus grows exponentially, and a third time scale on which viral
growth slows and the endemically infected steady state is approached. Using the
quasi-steady-state approximation the model can be simplified to two ordinary
differential equations the summarize much of the dynamical behavior. We compute
the level of T cells in the endemically infected state and show how that level
varies with the parameters in the model. The model predicts that different viral
strains, characterized by generating differing numbers of infective virions
within infected T cells, can cause different amounts of T-cell depletion and
generate depletion at different rates. Two versions of the model are studied. In
one the source of T cells from precursors is constant, whereas in the other the
source of T cells decreases with viral load, mimicking the infection and killing
of T-cell precursors.(ABSTRACT TRUNCATED AT 400 WORDS)
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Perelson AS, Kirschner DE, De Boer R. (1993) - version=1.0
The original CellML model was created by:
Ethan Choi
mcho099@aucklanduni.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
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To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
-
Dynamics of HIV infection of CD4+ T cells.
- Perelson AS, Kirschner DE, De Boer R
- Mathematical biosciences , 3/ 1993 , Volume 114 , pages: 81-125 , PubMed ID: 8096155
- Theoretical Division, Los Alamos National Laboratory, New Mexico.
- We examine a model for the interaction of HIV with CD4+ T cells that considers four populations: uninfected T cells, latently infected T cells, actively infected T cells, and free virus. Using this model we show that many of the puzzling quantitative features of HIV infection can be explained simply. We also consider effects of AZT on viral growth and T-cell population dynamics. The model exhibits two steady states, an uninfected state in which no virus is present and an endemically infected state, in which virus and infected T cells are present. We show that if N, the number of infectious virions produced per actively infected T cell, is less a critical value, Ncrit, then the uninfected state is the only steady state in the nonnegative orthant, and this state is stable. For N > Ncrit, the uninfected state is unstable, and the endemically infected state can be either stable, or unstable and surrounded by a stable limit cycle. Using numerical bifurcation techniques we map out the parameter regimes of these various behaviors. oscillatory behavior seems to lie outside the region of biologically realistic parameter values. When the endemically infected state is stable, it is characterized by a reduced number of T cells compared with the uninfected state. Thus T-cell depletion occurs through the establishment of a new steady state. The dynamics of the establishment of this new steady state are examined both numerically and via the quasi-steady-state approximation. We develop approximations for the dynamics at early times in which the free virus rapidly binds to T cells, during an intermediate time scale in which the virus grows exponentially, and a third time scale on which viral growth slows and the endemically infected steady state is approached. Using the quasi-steady-state approximation the model can be simplified to two ordinary differential equations the summarize much of the dynamical behavior. We compute the level of T cells in the endemically infected state and show how that level varies with the parameters in the model. The model predicts that different viral strains, characterized by generating differing numbers of infective virions within infected T cells, can cause different amounts of T-cell depletion and generate depletion at different rates. Two versions of the model are studied. In one the source of T cells from precursors is constant, whereas in the other the source of T cells decreases with viral load, mimicking the infection and killing of T-cell precursors.(ABSTRACT TRUNCATED AT 400 WORDS)
Submitter of this revision: Mohammad Umer Sharif Shohan
Modellers: Camille Laibe, Mohammad Umer Sharif Shohan
Metadata information
isDescribedBy (1 statement)
hasTaxon (1 statement)
isVersionOf (2 statements)
occursIn (1 statement)
Connected external resources
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Model files |
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Perelson1993.xml | SBML L2V4 representation of Perelson1993_HIVinfection_CD4Tcells_ModelA | 43.16 KB | Preview | Download |
Additional files |
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MODEL1006230079-biopax2.owl | Auto-generated BioPAX (Level 2) | 1.06 KB | Preview | Download |
MODEL1006230079-biopax3.owl | Auto-generated BioPAX (Level 3) | 2.02 KB | Preview | Download |
MODEL1006230079.m | Auto-generated Octave file | 2.94 KB | Preview | Download |
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MODEL1006230079_url.xml | old xml file | 13.57 KB | Preview | Download |
MODEL1006230079_urn.xml | Auto-generated SBML file with URNs | 14.19 KB | Preview | Download |
Perelson1993.cps | COPASI version 4.24 (Build 197) representation of Perelson1993_HIVinfection_CD4Tcells_ModelA | 74.03 KB | Preview | Download |
Perelson1993.sedml | SEDML L1V2 representation of Perelson1993_HIVinfection_CD4Tcells_ModelA | 3.70 KB | Preview | Download |
- Model originally submitted by : Camille Laibe
- Submitted: Jun 23, 2010 10:12:28 AM
- Last Modified: Nov 25, 2019 2:10:39 PM
Revisions
-
Version: 5
- Submitted on: Nov 25, 2019 2:10:39 PM
- Submitted by: Mohammad Umer Sharif Shohan
- With comment: Automatically added model identifier BIOMD0000000874
-
Version: 2
- Submitted on: Jun 25, 2010 2:37:31 PM
- Submitted by: Camille Laibe
- With comment: Current version of Perelson1993_HIVinfection_CD4Tcells_ModelA
-
Version: 1
- Submitted on: Jun 23, 2010 10:12:28 AM
- Submitted by: Camille Laibe
- With comment: Original import of Perelson1993_HIVinfection_CD4Tcells_ModelA
(*) You might be seeing discontinuous
revisions as only public revisions are displayed here. Any private revisions
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: Variable used inside SBML models
Species | Initial Concentration/Amount |
---|---|
T 1 P01730 |
0.0 mol |
T P01730 |
1000.0 mol |
T 2 P01730 |
0.0 mol |
V | 0.001 mol |
Reactions | Rate | Parameters |
---|---|---|
=> T_1; V, T | COMpartment*k_1*V*T | k_1 = 2.4E-5 |
=> T | COMpartment*(s+r*T) | s = 10.0; r = 0.03 |
T_1 => | COMpartment*(mu_T*T_1+k_2*T_1) | mu_T = 0.02; k_2 = 0.003 |
T => ; V, T_1, T_2 | COMpartment*(mu_T*T+k_1*V*T+r*T*(T+T_1+T_2)/T_max) | k_1 = 2.4E-5; mu_T = 0.02; T_max = 1500.0; r = 0.03 |
=> T_2; T_1 | COMpartment*k_2*T_1 | k_2 = 0.003 |
T_2 => | COMpartment*mu_b*T_2 | mu_b = 0.24 |
=> V; T_2 | COMpartment*N*mu_b*T_2 | N = 1000.0; mu_b = 0.24 |
V => ; T | COMpartment*(k_1*V*T+mu_V*V) | k_1 = 2.4E-5; mu_V = 2.4 |
(added: 25 Nov 2019, 14:09:21, updated: 25 Nov 2019, 14:09:21)