A hybrid stochastic-deterministic approach to explore multiple infection and evolution in HIV

Abstract To study viral evolutionary processes within patients, mathematical models have been instrumental. Yet, the need for stochastic simulations of minority mutant dynamics can pose computational challenges, especially in heterogeneous systems where very large and very small subpopulations coexi...

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Vydané v:bioRxiv
Hlavní autori: Kreger, Jesse, Komarova, Natalia L, Wodarz, Dominik
Médium: Paper
Jazyk:English
Vydavateľské údaje: Cold Spring Harbor Cold Spring Harbor Laboratory Press 16.02.2021
Cold Spring Harbor Laboratory
Vydanie:1.2
Predmet:
Cell size
Complementation
Computer applications
Disease transmission
Evolution
Evolutionary Biology
Genetic diversity
Genomes
HIV
Human immunodeficiency virus
Infections
Mathematical models
Mutants
Recombination
Synaptic transmission
Viruses
ISSN:2692-8205, 2692-8205
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Popis
Shrnutí:Abstract To study viral evolutionary processes within patients, mathematical models have been instrumental. Yet, the need for stochastic simulations of minority mutant dynamics can pose computational challenges, especially in heterogeneous systems where very large and very small subpopulations coexist. Here, we describe a hybrid stochastic-deterministic algorithm to simulate mutant evolution in large viral populations, such as acute HIV-1 infection, and further include the multiple infection of cells. We demonstrate that the hybrid method can approximate the fully stochastic dynamics with sufficient accuracy at a fraction of the computational time, and quantify evolutionary end points that cannot be expressed by deterministic models, such as the mutant distribution or the probability of mutant existence at a given infected cell population size. We apply this method to study the role of multiple infection and intracellular interactions among different virus strains (such as complementation and interference) for mutant evolution. Multiple infection is predicted to increase the number of mutants at a given infected cell population size, due to a larger number of infection events. We further find that viral complementation can significantly enhance the spread of disadvantageous mutants, but only in select circumstances: it requires the occurrence of direct cell-to-cell transmission through virological synapses, as well as a substantial fitness disadvantage of the mutant, most likely corresponding to defective virus particles. This, however, likely has strong biological consequences because defective viruses can carry genetic diversity that can be incorporated into functional virus genomes via recombination. Through this mechanism, synaptic transmission in HIV might promote virus evolvability. Competing Interest Statement The authors have declared no competing interest.
Bibliografia:SourceType-Working Papers-1
ObjectType-Working Paper/Pre-Print-1
content type line 50
Competing Interest Statement: The authors have declared no competing interest.
ISSN:2692-8205
2692-8205
DOI:10.1101/2020.08.30.274142