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Life cycle process dependencies of positive-sense RNA viruses suggest strategies for inhibiting productive cellular infection

Chhajer, H and Rizvi, VA and Roy, R (2021) Life cycle process dependencies of positive-sense RNA viruses suggest strategies for inhibiting productive cellular infection. In: Journal of the Royal Society Interface, 18 (184).

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Official URL: https://doi.org/10.1098/rsif.2021.0401


Life cycle processes of positive-strand (+)RNA viruses are broadly conserved across families, yet they employ different strategies to grow in the cell. Using a generalized dynamical model for intracellular (+)RNA virus growth, we decipher these life cycle determinants and their dependencies for several viruses and parse the effects of viral mutations, drugs and host cell permissivity. We show that poliovirus employs rapid replication and virus assembly, whereas the Japanese encephalitis virus leverages its higher rate of translation and efficient cellular reorganization compared to the hepatitis C virus. Stochastic simulations demonstrate infection extinction if all seeding (inoculating) viral RNA degrade before establishing robust replication critical for infection. The probability of this productive cellular infection, 'cellular infectivity', is affected by virus-host processes and defined by early life cycle events and viral seeding. An increase in cytoplasmic RNA degradation and delay in vesicular compartment formation reduces infectivity, more so when combined. Synergy among these parameters in limiting (+)RNA virus infection as predicted by our model suggests new avenues for inhibiting infections by targeting the early life cycle bottlenecks. © 2021 The Author(s).

Item Type: Journal Article
Publication: Journal of the Royal Society Interface
Publisher: Royal Society Publishing
Additional Information: The copyright for this article belongs to the Authors.
Keywords: Cell proliferation; Life cycle; RNA; Stochastic models; Viruses, Cellulars; Compartment formation dynamic; Formation dynamics; Life cycle model; Positive sense RNA virus; RNA virus; Stochastic fate of infection; Stochastics; Synergy in virus inhibition; Viral intracellular life cycle model, Stochastic systems, single stranded RNA; virus RNA; virus RNA, Article; controlled study; host cell; Huh-7 cell line; Japanese encephalitis virus; life cycle; mathematical model; Murine hepatitis virus; nonhuman; positive-strand RNA virus; ribosome; RNA degradation; virus infection; virus particle; virus replication; virus virulence; animal; genetics; human; life cycle stage; RNA virus, Animals; Humans; Life Cycle Stages; Positive-Strand RNA Viruses; RNA Viruses; RNA, Viral; Virus Replication
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Division of Mechanical Sciences > Chemical Engineering
Date Deposited: 01 Jun 2023 09:32
Last Modified: 01 Jun 2023 09:32
URI: https://eprints.iisc.ac.in/id/eprint/81725

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