Multiple HIV-1 Infection of cells and the evolutionary dynamics of cytotoxic t lymphocyte escape mutants

Dominik Wodarz, David Levy

Research output: Contribution to journalArticle

Abstract

Cytotoxic T lymphocytes (CTL) are an important branch of the immune system, killing virus-infected cells. Many viruses can mutate so that infected cells are not killed by CTL anymore. This escape can contribute to virus persistence and disease. A prominent example is HIV-1. The evolutionary dynamics of CTL escape mutants in vivo have been studied experimentally and mathematically, assuming that a cell can only be infected with one HIV particle at a time. However, according to data, multiple virus particles frequently infect the same cell, a process called coinfection. Here, we study the evolutionary dynamics of CTL escape mutants in the context of coinfection. A mathematical model suggests that an intermediate strength of the CTL response against the wild-type is most detrimental for an escape mutant, minimizing overall virus load and even leading to its extinction. A weaker or, paradoxically, stronger CTL response against the wild-type both lead to the persistence of the escape mutant and higher virus load. It is hypothesized that an intermediate strength of the CTL response, and thus the suboptimal virus suppression observed in HIV-1 infection, might be adaptive to minimize the impact of existing CTL escape mutants on overall virus load.

Original languageEnglish (US)
Pages (from-to)2326-2339
Number of pages14
JournalEvolution
Volume63
Issue number9
DOIs
StatePublished - Sep 2009

Fingerprint

cytotoxic T-lymphocytes
Cytotoxic T-Lymphocytes
human immunodeficiency virus
Human immunodeficiency virus 1
HIV Infections
HIV-1
virus
lymphocytes
Lymphocytes
mutants
Viruses
infection
viral load
cells
viruses
Coinfection
mixed infection
persistence
virus particle
immune system

Keywords

  • Coinfection
  • Disease progression
  • Evolutionary dynamics
  • HIV
  • Immune escape
  • Mathematical models

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Ecology, Evolution, Behavior and Systematics
  • Genetics

Cite this

Multiple HIV-1 Infection of cells and the evolutionary dynamics of cytotoxic t lymphocyte escape mutants. / Wodarz, Dominik; Levy, David.

In: Evolution, Vol. 63, No. 9, 09.2009, p. 2326-2339.

Research output: Contribution to journalArticle

@article{719fba78609340ba95fae4240d71f245,
title = "Multiple HIV-1 Infection of cells and the evolutionary dynamics of cytotoxic t lymphocyte escape mutants",
abstract = "Cytotoxic T lymphocytes (CTL) are an important branch of the immune system, killing virus-infected cells. Many viruses can mutate so that infected cells are not killed by CTL anymore. This escape can contribute to virus persistence and disease. A prominent example is HIV-1. The evolutionary dynamics of CTL escape mutants in vivo have been studied experimentally and mathematically, assuming that a cell can only be infected with one HIV particle at a time. However, according to data, multiple virus particles frequently infect the same cell, a process called coinfection. Here, we study the evolutionary dynamics of CTL escape mutants in the context of coinfection. A mathematical model suggests that an intermediate strength of the CTL response against the wild-type is most detrimental for an escape mutant, minimizing overall virus load and even leading to its extinction. A weaker or, paradoxically, stronger CTL response against the wild-type both lead to the persistence of the escape mutant and higher virus load. It is hypothesized that an intermediate strength of the CTL response, and thus the suboptimal virus suppression observed in HIV-1 infection, might be adaptive to minimize the impact of existing CTL escape mutants on overall virus load.",
keywords = "Coinfection, Disease progression, Evolutionary dynamics, HIV, Immune escape, Mathematical models",
author = "Dominik Wodarz and David Levy",
year = "2009",
month = "9",
doi = "10.1111/j.1558-5646.2009.00727.x",
language = "English (US)",
volume = "63",
pages = "2326--2339",
journal = "Evolution; international journal of organic evolution",
issn = "0014-3820",
publisher = "Society for the Study of Evolution",
number = "9",

}

TY - JOUR

T1 - Multiple HIV-1 Infection of cells and the evolutionary dynamics of cytotoxic t lymphocyte escape mutants

AU - Wodarz, Dominik

AU - Levy, David

PY - 2009/9

Y1 - 2009/9

N2 - Cytotoxic T lymphocytes (CTL) are an important branch of the immune system, killing virus-infected cells. Many viruses can mutate so that infected cells are not killed by CTL anymore. This escape can contribute to virus persistence and disease. A prominent example is HIV-1. The evolutionary dynamics of CTL escape mutants in vivo have been studied experimentally and mathematically, assuming that a cell can only be infected with one HIV particle at a time. However, according to data, multiple virus particles frequently infect the same cell, a process called coinfection. Here, we study the evolutionary dynamics of CTL escape mutants in the context of coinfection. A mathematical model suggests that an intermediate strength of the CTL response against the wild-type is most detrimental for an escape mutant, minimizing overall virus load and even leading to its extinction. A weaker or, paradoxically, stronger CTL response against the wild-type both lead to the persistence of the escape mutant and higher virus load. It is hypothesized that an intermediate strength of the CTL response, and thus the suboptimal virus suppression observed in HIV-1 infection, might be adaptive to minimize the impact of existing CTL escape mutants on overall virus load.

AB - Cytotoxic T lymphocytes (CTL) are an important branch of the immune system, killing virus-infected cells. Many viruses can mutate so that infected cells are not killed by CTL anymore. This escape can contribute to virus persistence and disease. A prominent example is HIV-1. The evolutionary dynamics of CTL escape mutants in vivo have been studied experimentally and mathematically, assuming that a cell can only be infected with one HIV particle at a time. However, according to data, multiple virus particles frequently infect the same cell, a process called coinfection. Here, we study the evolutionary dynamics of CTL escape mutants in the context of coinfection. A mathematical model suggests that an intermediate strength of the CTL response against the wild-type is most detrimental for an escape mutant, minimizing overall virus load and even leading to its extinction. A weaker or, paradoxically, stronger CTL response against the wild-type both lead to the persistence of the escape mutant and higher virus load. It is hypothesized that an intermediate strength of the CTL response, and thus the suboptimal virus suppression observed in HIV-1 infection, might be adaptive to minimize the impact of existing CTL escape mutants on overall virus load.

KW - Coinfection

KW - Disease progression

KW - Evolutionary dynamics

KW - HIV

KW - Immune escape

KW - Mathematical models

UR - http://www.scopus.com/inward/record.url?scp=69249195777&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=69249195777&partnerID=8YFLogxK

U2 - 10.1111/j.1558-5646.2009.00727.x

DO - 10.1111/j.1558-5646.2009.00727.x

M3 - Article

C2 - 19486149

AN - SCOPUS:69249195777

VL - 63

SP - 2326

EP - 2339

JO - Evolution; international journal of organic evolution

JF - Evolution; international journal of organic evolution

SN - 0014-3820

IS - 9

ER -