Effect of different modes of viral spread on the dynamics of multiply infected cells in human immunodeficiency virus infection

Dominik Wodarz, David Levy

Research output: Contribution to journalArticle

Abstract

Infection of individual cells with more than one HIV particle is an important feature of HIV replication, which may contribute to HIV pathogenesis via the occurrence of recombination, viral complementation and other outcomes that influence HIV replication and evolutionary dynamics. A previous mathematical model of co-infection has shown that the number of cells infected with i viruses correlates with the ith power of the singly infected cell population, and this has partly been observed in experiments. This model, however, assumed that virus spread from cell to cell occurs only via free virus particles, and that viruses and cells mix perfectly. Here, we introduce a cellular automaton model that takes into account different modes of virus spread among cells, including cell to cell transmission via the virological synapse, and spatially constrained virus spread. In these scenarios, it is found that the number of multiply infected cells correlates linearly with the number of singly infected cells, meaning that coinfection plays a greater role at lower virus loads. The model further indicates that current experimental systems that are used to study co-infection dynamics fail to reflect the true dynamics of multiply infected cells under these specific assumptions, and that new experimental techniques need to be designed to distinguish between the different assumptions.

Original languageEnglish (US)
Pages (from-to)289-300
Number of pages12
JournalJournal of the Royal Society Interface
Volume8
Issue number55
DOIs
StatePublished - Feb 6 2011

Fingerprint

Virus Diseases
Viruses
HIV
Coinfection
Cells
Cellular automata
Mathematical models
Virion
Synapses
Genetic Recombination
Theoretical Models
Cell Count
Experiments

Keywords

  • HIV
  • Mathematical model
  • Multiple infection
  • Spatial
  • Virus spread

ASJC Scopus subject areas

  • Biophysics
  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Biomaterials
  • Biochemistry

Cite this

@article{05add2045a814c67a93e36d8c9edeb8e,
title = "Effect of different modes of viral spread on the dynamics of multiply infected cells in human immunodeficiency virus infection",
abstract = "Infection of individual cells with more than one HIV particle is an important feature of HIV replication, which may contribute to HIV pathogenesis via the occurrence of recombination, viral complementation and other outcomes that influence HIV replication and evolutionary dynamics. A previous mathematical model of co-infection has shown that the number of cells infected with i viruses correlates with the ith power of the singly infected cell population, and this has partly been observed in experiments. This model, however, assumed that virus spread from cell to cell occurs only via free virus particles, and that viruses and cells mix perfectly. Here, we introduce a cellular automaton model that takes into account different modes of virus spread among cells, including cell to cell transmission via the virological synapse, and spatially constrained virus spread. In these scenarios, it is found that the number of multiply infected cells correlates linearly with the number of singly infected cells, meaning that coinfection plays a greater role at lower virus loads. The model further indicates that current experimental systems that are used to study co-infection dynamics fail to reflect the true dynamics of multiply infected cells under these specific assumptions, and that new experimental techniques need to be designed to distinguish between the different assumptions.",
keywords = "HIV, Mathematical model, Multiple infection, Spatial, Virus spread",
author = "Dominik Wodarz and David Levy",
year = "2011",
month = "2",
day = "6",
doi = "10.1098/rsif.2010.0266",
language = "English (US)",
volume = "8",
pages = "289--300",
journal = "Journal of the Royal Society Interface",
issn = "1742-5689",
publisher = "Royal Society of London",
number = "55",

}

TY - JOUR

T1 - Effect of different modes of viral spread on the dynamics of multiply infected cells in human immunodeficiency virus infection

AU - Wodarz, Dominik

AU - Levy, David

PY - 2011/2/6

Y1 - 2011/2/6

N2 - Infection of individual cells with more than one HIV particle is an important feature of HIV replication, which may contribute to HIV pathogenesis via the occurrence of recombination, viral complementation and other outcomes that influence HIV replication and evolutionary dynamics. A previous mathematical model of co-infection has shown that the number of cells infected with i viruses correlates with the ith power of the singly infected cell population, and this has partly been observed in experiments. This model, however, assumed that virus spread from cell to cell occurs only via free virus particles, and that viruses and cells mix perfectly. Here, we introduce a cellular automaton model that takes into account different modes of virus spread among cells, including cell to cell transmission via the virological synapse, and spatially constrained virus spread. In these scenarios, it is found that the number of multiply infected cells correlates linearly with the number of singly infected cells, meaning that coinfection plays a greater role at lower virus loads. The model further indicates that current experimental systems that are used to study co-infection dynamics fail to reflect the true dynamics of multiply infected cells under these specific assumptions, and that new experimental techniques need to be designed to distinguish between the different assumptions.

AB - Infection of individual cells with more than one HIV particle is an important feature of HIV replication, which may contribute to HIV pathogenesis via the occurrence of recombination, viral complementation and other outcomes that influence HIV replication and evolutionary dynamics. A previous mathematical model of co-infection has shown that the number of cells infected with i viruses correlates with the ith power of the singly infected cell population, and this has partly been observed in experiments. This model, however, assumed that virus spread from cell to cell occurs only via free virus particles, and that viruses and cells mix perfectly. Here, we introduce a cellular automaton model that takes into account different modes of virus spread among cells, including cell to cell transmission via the virological synapse, and spatially constrained virus spread. In these scenarios, it is found that the number of multiply infected cells correlates linearly with the number of singly infected cells, meaning that coinfection plays a greater role at lower virus loads. The model further indicates that current experimental systems that are used to study co-infection dynamics fail to reflect the true dynamics of multiply infected cells under these specific assumptions, and that new experimental techniques need to be designed to distinguish between the different assumptions.

KW - HIV

KW - Mathematical model

KW - Multiple infection

KW - Spatial

KW - Virus spread

UR - http://www.scopus.com/inward/record.url?scp=78650829832&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650829832&partnerID=8YFLogxK

U2 - 10.1098/rsif.2010.0266

DO - 10.1098/rsif.2010.0266

M3 - Article

VL - 8

SP - 289

EP - 300

JO - Journal of the Royal Society Interface

JF - Journal of the Royal Society Interface

SN - 1742-5689

IS - 55

ER -