Noise-induced bistability in the quasi-neutral coexistence of viral RNAs under different replication modes

Author:

Sardanyés Josep12,Arderiu Andreu1,Elena Santiago F.345,Alarcón Tomás1267

Affiliation:

1. Centre de Recerca Matemàtica, Campus de Bellaterra, Edifici C, 08193 Bellaterra, Barcelona, Spain

2. Barcelona Graduate School of Mathematics (BGSMath), Campus de Bellaterra, Edifici C, 08193 Bellaterra, Barcelona, Spain

3. Instituto de Biología Molecular y Celular de Plantas (IBMCP), Consejo Superior de Investigaciones Científicas-Universitat Politècnica de València, Ingeniero Fausto Elio s/n, 46022 València, Spain

4. Instituto de Biología Integrativa de Sistemas (I2SysBio), Consejo Superior de Investigaciones Científicas-Universitat de València, Parc Científic UV, Catedrático José Beltrán 2, Paterna, 46980 València, Spain

5. Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM 87501, USA

6. ICREA, Pg. Lluis Companys 23, 08010 Barcelona, Spain

7. Departament de Matemàtiques, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain

Abstract

Evolutionary and dynamical investigations into real viral populations indicate that RNA replication can range between the two extremes represented by so-called ‘stamping machine replication’ (SMR) and ‘geometric replication’ (GR). The impact of asymmetries in replication for single-stranded (+) sense RNA viruses has been mainly studied with deterministic models. However, viral replication should be better described by including stochasticity, as the cell infection process is typically initiated with a very small number of RNA macromolecules, and thus largely influenced by intrinsic noise. Under appropriate conditions, deterministic theoretical descriptions of viral RNA replication predict a quasi-neutral coexistence scenario, with a line of fixed points involving different strands' equilibrium ratios depending on the initial conditions. Recent research into the quasi-neutral coexistence in two competing populations reveals that stochastic fluctuations fundamentally alter the mean-field scenario, and one of the two species outcompetes the other. In this article, we study this phenomenon for viral RNA replication modes by means of stochastic simulations and a diffusion approximation. Our results reveal that noise has a strong impact on the amplification of viral RNAs, also causing the emergence of noise-induced bistability. We provide analytical criteria for the dominance of (+) sense strands depending on the initial populations on the line of equilibria, which are in agreement with direct stochastic simulation results. The biological implications of this noise-driven mechanism are discussed within the framework of the evolutionary dynamics of RNA viruses with different modes of replication.

Funder

la caixa Foundation

Publisher

The Royal Society

Subject

Biomedical Engineering,Biochemistry,Biomaterials,Bioengineering,Biophysics,Biotechnology

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