Lim2014 - HTLV-I infection A dynamic struggle between viral persistence and host immunity

  public model
Model Identifier
BIOMD0000000887
Short description 
This is a four-dimensional, non-linear system of ordinary differential equations that describes the dynamic interactions among viral expression, infected target cell activation, and the HTLV-I-specific CTL response.
Format
SBML (L2V4)
Related Publication
  • HTLV-I infection: a dynamic struggle between viral persistence and host immunity.
  • Lim AG, Maini PK
  • Journal of theoretical biology , 7/ 2014 , Volume 352 , pages: 92-108 , PubMed ID: 24583256
  • Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Andrew Wiles Building, Radcliffe Observatory Quarter, Woodstock Road, Oxford OX2 6GG, UK. Electronic address: aaron.lim@maths.ox.ac.uk.
  • Human T-lymphotropic virus type I (HTLV-I) causes chronic infection for which there is no cure or neutralising vaccine. HTLV-I has been clinically linked to the development of adult T-cell leukaemia/lymphoma (ATL), an aggressive blood cancer, and HAM/TSP, a progressive neurological and inflammatory disease. Infected individuals typically mount a large, persistently activated CD8(+) cytotoxic T-lymphocyte (CTL) response against HTLV-I-infected cells, but ultimately fail to effectively eliminate the virus. Moreover, the identification of determinants to disease manifestation has thus far been elusive. A key issue in current HTLV-I research is to better understand the dynamic interaction between persistent infection by HTLV-I and virus-specific host immunity. Recent experimental hypotheses for the persistence of HTLV-I in vivo have led to the development of mathematical models illuminating the balance between proviral latency and activation in the target cell population. We investigate the role of a constantly changing anti-viral immune environment acting in response to the effects of infected T-cell activation and subsequent viral expression. The resulting model is a four-dimensional, non-linear system of ordinary differential equations that describes the dynamic interactions among viral expression, infected target cell activation, and the HTLV-I-specific CTL response. The global dynamics of the model is established through the construction of appropriate Lyapunov functions. Examining the particular roles of viral expression and host immunity during the chronic phase of HTLV-I infection offers important insights regarding the evolution of viral persistence and proposes a hypothesis for pathogenesis.
Contributors
Submitter of the first revision: Johannes Meyer
Submitter of this revision: Rahuman Sheriff
Modellers: Rahuman Sheriff, Johannes Meyer

Metadata information

is (2 statements)
BioModels Database BIOMD0000000887
BioModels Database MODEL1912100003

isDescribedBy (1 statement)
PubMed 24583256

isDerivedFrom (1 statement)
PubMed 21509627

hasTaxon (1 statement)
Taxonomy Homo sapiens

hasProperty (3 statements)
Mathematical Modelling Ontology Ordinary differential equation model
NCIt Immune Response Process
NCIt HTLV-1

Curation status
Curated
Tags

Connected external resources

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Name Description Size Actions

Model files
Lim2014.xml SBML L2V4 Representation of Lim2014 - HTLV-I infection A dynamic struggle between viral persistence and host immunity 37.36 KB Preview | Download

Additional files
Lim2014.cps COPASI file of Lim2014 - HTLV-I infection A dynamic struggle between viral persistence and host immunity 65.13 KB Preview | Download
Lim2014.sedml SED-ML file of Lim2014 - HTLV-I infection A dynamic struggle between viral persistence and host immunity 2.18 KB Preview | Download

  • Model originally submitted by : Johannes Meyer
  • Submitted: Dec 10, 2019 3:07:44 PM
  • Last Modified: Oct 8, 2021 8:02:48 AM
Revisions
  • Version: 4 public model Download this version
    • Submitted on: Oct 8, 2021 8:02:48 AM
    • Submitted by: Rahuman Sheriff
    • With comment: Automatically added model identifier BIOMD0000000887
  • Version: 2 public model Download this version
    • Submitted on: Dec 10, 2019 3:08:35 PM
    • Submitted by: Johannes Meyer
    • With comment: Automatically added model identifier BIOMD0000000887
  • Version: 1 public model Download this version
    • Submitted on: Dec 10, 2019 3:07:44 PM
    • Submitted by: Johannes Meyer
    • With comment: Import of Lim2014 - HTLV-I infection A dynamic struggle between viral persistence and host immunity

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
u

CD4-positive helper T cell 		0.1 item
x

CD4-positive helper T cell ; infected cell 		850.0 item
y

CD4-positive helper T cell ; infected cell 		0.5 item
Reactions
Reactions Rate Parameters
u => compartment*mu_2*u mu_2 = 0.03
=> u; y compartment*r*y r = 0.011
x => u; y compartment*beta*x*y beta = 0.001
x => compartment*mu_1*x mu_1 = 0.012
y => compartment*mu_3*y mu_3 = 0.03
=> x compartment*lambda lambda = 10.0
y => ; z compartment*gamma*y*z gamma = 0.029
u => y compartment*tau*u tau = 0.003
Curator's comment:
(added: 10 Dec 2019, 15:08:20, updated: 10 Dec 2019, 15:08:20)
Reproduced plot of Figure 2(c) in the original publication. Model simulated and plot produced using COPASI 4.24 (Build 197).