Competition of SARS-CoV-2 Variants in Cell Culture and Tissue: Wins the Fastest Viral Autowave

Replication of viruses in living tissues and cell cultures is a “number game” involving complex biological processes (cell infection, virus replication inside infected cell, cell death, viral degradation) as well as transport processes limiting virus spatial propagation. In epithelial tissues and im...

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Main Authors: Alexey Tokarev, Anastasia Mozokhina, Vitaly Volpert
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/10/7/995
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author Alexey Tokarev
Anastasia Mozokhina
Vitaly Volpert
author_facet Alexey Tokarev
Anastasia Mozokhina
Vitaly Volpert
author_sort Alexey Tokarev
collection DOAJ
description Replication of viruses in living tissues and cell cultures is a “number game” involving complex biological processes (cell infection, virus replication inside infected cell, cell death, viral degradation) as well as transport processes limiting virus spatial propagation. In epithelial tissues and immovable cell cultures, viral particles are basically transported via Brownian diffusion. Highly non-linear kinetics of viral replication combined with diffusion limitation lead to spatial propagation of infection as a moving front switching from zero to high local viral concentration, the behavior typical of spatially distributed excitable media. We propose a mathematical model of viral infection propagation in cell cultures and tissues under the diffusion limitation. The model is based on the reaction–diffusion equations describing the concentration of uninfected cells, exposed cells (infected but still not shedding the virus), virus-shedding cells, and free virus. We obtain the expressions for the viral replication number, which determines the condition for spatial infection progression, and for the final concentration of uninfected cells. We determine analytically the speed of spatial infection propagation and validate it numerically. We calibrate the model to recent experimental data on SARS-CoV-2 Delta and Omicron variant replication in human nasal epithelial cells. In the case of competition of two virus variants in the same cell culture, the variant with larger individual spreading speed wins the competition and eliminates another one. These results give new insights concerning the emergence of new variants and their spread in the population.
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spelling doaj.art-1fe3c2d0529e486f9f640707aec0c1622023-12-01T22:46:00ZengMDPI AGVaccines2076-393X2022-06-0110799510.3390/vaccines10070995Competition of SARS-CoV-2 Variants in Cell Culture and Tissue: Wins the Fastest Viral AutowaveAlexey Tokarev0Anastasia Mozokhina1Vitaly Volpert2S.M. Nikolskii Mathematical Institute, Peoples Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya Street, 117198 Moscow, RussiaS.M. Nikolskii Mathematical Institute, Peoples Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya Street, 117198 Moscow, RussiaS.M. Nikolskii Mathematical Institute, Peoples Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya Street, 117198 Moscow, RussiaReplication of viruses in living tissues and cell cultures is a “number game” involving complex biological processes (cell infection, virus replication inside infected cell, cell death, viral degradation) as well as transport processes limiting virus spatial propagation. In epithelial tissues and immovable cell cultures, viral particles are basically transported via Brownian diffusion. Highly non-linear kinetics of viral replication combined with diffusion limitation lead to spatial propagation of infection as a moving front switching from zero to high local viral concentration, the behavior typical of spatially distributed excitable media. We propose a mathematical model of viral infection propagation in cell cultures and tissues under the diffusion limitation. The model is based on the reaction–diffusion equations describing the concentration of uninfected cells, exposed cells (infected but still not shedding the virus), virus-shedding cells, and free virus. We obtain the expressions for the viral replication number, which determines the condition for spatial infection progression, and for the final concentration of uninfected cells. We determine analytically the speed of spatial infection propagation and validate it numerically. We calibrate the model to recent experimental data on SARS-CoV-2 Delta and Omicron variant replication in human nasal epithelial cells. In the case of competition of two virus variants in the same cell culture, the variant with larger individual spreading speed wins the competition and eliminates another one. These results give new insights concerning the emergence of new variants and their spread in the population.https://www.mdpi.com/2076-393X/10/7/995viral infectioncompetition of viral strainsreaction–diffusion systemsautowavesmathematical modeling and analysis
spellingShingle Alexey Tokarev
Anastasia Mozokhina
Vitaly Volpert
Competition of SARS-CoV-2 Variants in Cell Culture and Tissue: Wins the Fastest Viral Autowave
Vaccines
viral infection
competition of viral strains
reaction–diffusion systems
autowaves
mathematical modeling and analysis
title Competition of SARS-CoV-2 Variants in Cell Culture and Tissue: Wins the Fastest Viral Autowave
title_full Competition of SARS-CoV-2 Variants in Cell Culture and Tissue: Wins the Fastest Viral Autowave
title_fullStr Competition of SARS-CoV-2 Variants in Cell Culture and Tissue: Wins the Fastest Viral Autowave
title_full_unstemmed Competition of SARS-CoV-2 Variants in Cell Culture and Tissue: Wins the Fastest Viral Autowave
title_short Competition of SARS-CoV-2 Variants in Cell Culture and Tissue: Wins the Fastest Viral Autowave
title_sort competition of sars cov 2 variants in cell culture and tissue wins the fastest viral autowave
topic viral infection
competition of viral strains
reaction–diffusion systems
autowaves
mathematical modeling and analysis
url https://www.mdpi.com/2076-393X/10/7/995
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