Dynamics of HIV-1 coinfection in different susceptible target cell populations during cell-free infection

Yusuke Ito, Alexandra Tauzin, Azaria Remion, Keisuke Ejima, Fabrizio Mammano, Shingo Iwami

Research output: Contribution to journalArticle

Abstract

HIV-1 mutations rapidly accumulate through genetic recombination events, which require the infection of a single cell by two virions (coinfection). Accumulation of mutations in the viral population may lead to immune escape and high-level drug resistance. The existence of cell subpopulations characterized by different susceptibility to HIV-1 infection has been proposed as an important parameter driving coinfection (Dang et al., 2004). While the mechanism and the quantification of HIV-1 coinfection have been recently investigated by mathematical models, the detailed dynamics of this process during cell-free infection remains elusive. In this study, we constructed ordinary differential equations considering the heterogeneity of target cell populations during cell-free infection in cell culture, and reproduced the cell culture experimental data. Our mathematical analyses showed that the presence of two differently susceptible target cell subpopulations could explain our experimental datasets, while increasing the number of subpopulations did not improve the fitting. In addition, we quantitatively demonstrated that cells infected by multiple viruses mainly accumulated from one cell subpopulation under cell-free infection conditions. In particular, the frequency of infection events in the more susceptible subpopulation was 6.11-higher than that from the other subpopulation, and 98.3% of coinfected cells emerged from the more susceptible subpopulation. Our mathematical-experimental approach is able to extract such a quantitative information, and can be easily applied to other virus infections.

Original languageEnglish
Pages (from-to)39-46
Number of pages8
JournalJournal of Theoretical Biology
Volume455
DOIs
Publication statusPublished - Oct 14 2018

Fingerprint

Health Services Needs and Demand
Cell Population
Human immunodeficiency virus 1
Coinfection
mixed infection
Viruses
Cell culture
Infection
HIV-1
Cells
Target
Cell
Ordinary differential equations
infection
cells
Mathematical models
Cell Culture
Pharmaceutical Preparations
Virus
Mutation

All Science Journal Classification (ASJC) codes

  • Statistics and Probability
  • Modelling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

Cite this

Dynamics of HIV-1 coinfection in different susceptible target cell populations during cell-free infection. / Ito, Yusuke; Tauzin, Alexandra; Remion, Azaria; Ejima, Keisuke; Mammano, Fabrizio; Iwami, Shingo.

In: Journal of Theoretical Biology, Vol. 455, 14.10.2018, p. 39-46.

Research output: Contribution to journalArticle

Ito, Yusuke ; Tauzin, Alexandra ; Remion, Azaria ; Ejima, Keisuke ; Mammano, Fabrizio ; Iwami, Shingo. / Dynamics of HIV-1 coinfection in different susceptible target cell populations during cell-free infection. In: Journal of Theoretical Biology. 2018 ; Vol. 455. pp. 39-46.
@article{fe04b897ca234e859012a6f9d02aaba1,
title = "Dynamics of HIV-1 coinfection in different susceptible target cell populations during cell-free infection",
abstract = "HIV-1 mutations rapidly accumulate through genetic recombination events, which require the infection of a single cell by two virions (coinfection). Accumulation of mutations in the viral population may lead to immune escape and high-level drug resistance. The existence of cell subpopulations characterized by different susceptibility to HIV-1 infection has been proposed as an important parameter driving coinfection (Dang et al., 2004). While the mechanism and the quantification of HIV-1 coinfection have been recently investigated by mathematical models, the detailed dynamics of this process during cell-free infection remains elusive. In this study, we constructed ordinary differential equations considering the heterogeneity of target cell populations during cell-free infection in cell culture, and reproduced the cell culture experimental data. Our mathematical analyses showed that the presence of two differently susceptible target cell subpopulations could explain our experimental datasets, while increasing the number of subpopulations did not improve the fitting. In addition, we quantitatively demonstrated that cells infected by multiple viruses mainly accumulated from one cell subpopulation under cell-free infection conditions. In particular, the frequency of infection events in the more susceptible subpopulation was 6.11-higher than that from the other subpopulation, and 98.3{\%} of coinfected cells emerged from the more susceptible subpopulation. Our mathematical-experimental approach is able to extract such a quantitative information, and can be easily applied to other virus infections.",
author = "Yusuke Ito and Alexandra Tauzin and Azaria Remion and Keisuke Ejima and Fabrizio Mammano and Shingo Iwami",
year = "2018",
month = "10",
day = "14",
doi = "10.1016/j.jtbi.2018.06.025",
language = "English",
volume = "455",
pages = "39--46",
journal = "Journal of Theoretical Biology",
issn = "0022-5193",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Dynamics of HIV-1 coinfection in different susceptible target cell populations during cell-free infection

AU - Ito, Yusuke

AU - Tauzin, Alexandra

AU - Remion, Azaria

AU - Ejima, Keisuke

AU - Mammano, Fabrizio

AU - Iwami, Shingo

PY - 2018/10/14

Y1 - 2018/10/14

N2 - HIV-1 mutations rapidly accumulate through genetic recombination events, which require the infection of a single cell by two virions (coinfection). Accumulation of mutations in the viral population may lead to immune escape and high-level drug resistance. The existence of cell subpopulations characterized by different susceptibility to HIV-1 infection has been proposed as an important parameter driving coinfection (Dang et al., 2004). While the mechanism and the quantification of HIV-1 coinfection have been recently investigated by mathematical models, the detailed dynamics of this process during cell-free infection remains elusive. In this study, we constructed ordinary differential equations considering the heterogeneity of target cell populations during cell-free infection in cell culture, and reproduced the cell culture experimental data. Our mathematical analyses showed that the presence of two differently susceptible target cell subpopulations could explain our experimental datasets, while increasing the number of subpopulations did not improve the fitting. In addition, we quantitatively demonstrated that cells infected by multiple viruses mainly accumulated from one cell subpopulation under cell-free infection conditions. In particular, the frequency of infection events in the more susceptible subpopulation was 6.11-higher than that from the other subpopulation, and 98.3% of coinfected cells emerged from the more susceptible subpopulation. Our mathematical-experimental approach is able to extract such a quantitative information, and can be easily applied to other virus infections.

AB - HIV-1 mutations rapidly accumulate through genetic recombination events, which require the infection of a single cell by two virions (coinfection). Accumulation of mutations in the viral population may lead to immune escape and high-level drug resistance. The existence of cell subpopulations characterized by different susceptibility to HIV-1 infection has been proposed as an important parameter driving coinfection (Dang et al., 2004). While the mechanism and the quantification of HIV-1 coinfection have been recently investigated by mathematical models, the detailed dynamics of this process during cell-free infection remains elusive. In this study, we constructed ordinary differential equations considering the heterogeneity of target cell populations during cell-free infection in cell culture, and reproduced the cell culture experimental data. Our mathematical analyses showed that the presence of two differently susceptible target cell subpopulations could explain our experimental datasets, while increasing the number of subpopulations did not improve the fitting. In addition, we quantitatively demonstrated that cells infected by multiple viruses mainly accumulated from one cell subpopulation under cell-free infection conditions. In particular, the frequency of infection events in the more susceptible subpopulation was 6.11-higher than that from the other subpopulation, and 98.3% of coinfected cells emerged from the more susceptible subpopulation. Our mathematical-experimental approach is able to extract such a quantitative information, and can be easily applied to other virus infections.

UR - http://www.scopus.com/inward/record.url?scp=85049749867&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049749867&partnerID=8YFLogxK

U2 - 10.1016/j.jtbi.2018.06.025

DO - 10.1016/j.jtbi.2018.06.025

M3 - Article

AN - SCOPUS:85049749867

VL - 455

SP - 39

EP - 46

JO - Journal of Theoretical Biology

JF - Journal of Theoretical Biology

SN - 0022-5193

ER -