Multiple HIV-1 infection of cells and the evolutionary dynamics of cytotoxic T lymphocyte escape mutants

Evolution; International Journal of Organic Evolution
Dominik Wodarz, David N Levy

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...Continue Reading

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Citations

Jun 14, 2013·Nucleic Acids Research·Kasandra BélangerMarc-André Langlois
Apr 12, 2012·Proceedings. Biological Sciences·Christian L Althaus, Rob J De Boer
Nov 17, 2012·PloS One·Carmen Lía MurallChris T Bauch
Jan 30, 2013·Mathematical Biosciences·Natalia L Komarova, Dominik Wodarz
Mar 15, 2015·Mathematical Biosciences·Dustin Phan, Dominik Wodarz
Jul 3, 2013·Scientific Reports·Natalia L KomarovaDominik Wodarz

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