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

Dominik Wodarz, David N. Levy

Research output: Contribution to journalArticlepeer-review

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

Keywords

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

ASJC Scopus subject areas

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

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