EXISTENCE AND DYNAMICS OF STRAINS IN A NONLOCAL REACTION-DIFFUSION MODEL OF VIRAL EVOLUTION

被引:10
|
作者
Bessonov, Nikolai [1 ]
Bocharov, Gennady [2 ,3 ,4 ]
Meyerhans, Andreas [5 ,6 ]
Popov, Vladimir [7 ]
Volpert, Vitaly [7 ,8 ,9 ]
机构
[1] Russian Acad Sci, Inst Problems Mech Engn, St Petersburg 199178, Russia
[2] Russian Acad Sci, Marchuk Inst Numer Math, Moscow 119991, Russia
[3] INM RAS, Moscow Ctr Fundamental & Appl Math, Moscow 119333, Russia
[4] Sechenov First Moscow State Med Univ, Moscow 119991, Russia
[5] ICREA, Pg Lluis Co 23, Barcelona 08010, Spain
[6] Univ Pompeu Fabra, Infect Biol Lab, Barcelona 08003, Spain
[7] Peoples Friendship Univ Russia, RUDN Univ, 6 Miklukho Maklaya St, Moscow 117198, Russia
[8] Univ Lyon 1, UMR 5208, Inst Camille Jordan, CNRS, Villeurbanne, France
[9] INRIA Lyon La Doua, INRIA Team Dracula, F-69603 Villeurbanne, France
基金
俄罗斯科学基金会;
关键词
virus density distribution; genotype; virus infection; immune response; resistance to treatment; nonlocal interaction; DRUG-RESISTANCE; TRAVELING-WAVES; ELLIPTIC-OPERATORS; EQUATION; VARIABILITY; EMERGENCE; RESPONSES; PATTERN;
D O I
10.1137/19M1282234
中图分类号
O29 [应用数学];
学科分类号
070104 ;
摘要
In this work, we develop a mathematical framework for predicting and quantifying virus diversity evolution during infection of a host organism. It is specified as a virus density distribution with respect to genotype and time governed by a reaction-diffusion integro-differential equation taking virus mutations, replication, and elimination by immune cells and medical treatment into account. Conditions for the existence of virus strains that correspond to localized density distributions in the space of genotypes are determined. It is shown that common viral evolutionary traits like diversification and extinction are driven by nonlocal interactions via immune responses, target-cell competition, and therapy. This provides us with a mechanistic explanation for clinically relevant properties like immune escape and drug resistance selection, and allows us to link virus genotypes to phenotypes.
引用
收藏
页码:107 / 128
页数:22
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