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Quantification of Ebola virus replication kinetics in vitro

Author

Listed:
  • Laura E Liao
  • Jonathan Carruthers
  • Sophie J Smither
  • CL4 Virology Team
  • Simon A Weller
  • Diane Williamson
  • Thomas R Laws
  • Isabel García-Dorival
  • Julian Hiscox
  • Benjamin P Holder
  • Catherine A A Beauchemin
  • Alan S Perelson
  • Martín López-García
  • Grant Lythe
  • John N Barr
  • Carmen Molina-París

Abstract

Mathematical modelling has successfully been used to provide quantitative descriptions of many viral infections, but for the Ebola virus, which requires biosafety level 4 facilities for experimentation, modelling can play a crucial role. Ebola virus modelling efforts have primarily focused on in vivo virus kinetics, e.g., in animal models, to aid the development of antivirals and vaccines. But, thus far, these studies have not yielded a detailed specification of the infection cycle, which could provide a foundational description of the virus kinetics and thus a deeper understanding of their clinical manifestation. Here, we obtain a diverse experimental data set of the Ebola virus infection in vitro, and then make use of Bayesian inference methods to fully identify parameters in a mathematical model of the infection. Our results provide insights into the distribution of time an infected cell spends in the eclipse phase (the period between infection and the start of virus production), as well as the rate at which infectious virions lose infectivity. We suggest how these results can be used in future models to describe co-infection with defective interfering particles, which are an emerging alternative therapeutic.Author summary: The two deadliest Ebola virus epidemics have both occurred in the past five years, with one of these epidemics still ongoing. Mathematical modelling has already provided insights into the spread of disease at the population level as well as the effect of antiviral therapy in Ebola virus-infected animals. However, a quantitative description of the replication cycle is still missing. Here, we report results from a set of in vitro experiments involving infection with the Ecran strain of Ebola virus. By parameterizing a mathematical model, we are able to determine robust estimates for the duration of the replication cycle, the infectious burst size, and the viral clearance rate.

Suggested Citation

  • Laura E Liao & Jonathan Carruthers & Sophie J Smither & CL4 Virology Team & Simon A Weller & Diane Williamson & Thomas R Laws & Isabel García-Dorival & Julian Hiscox & Benjamin P Holder & Catherine A , 2020. "Quantification of Ebola virus replication kinetics in vitro," PLOS Computational Biology, Public Library of Science, vol. 16(11), pages 1-15, November.
    • Handle: RePEc:plo:pcbi00:1008375
    DOI: 10.1371/journal.pcbi.1008375
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    References listed on IDEAS

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    1. Vincent Madelain & Sylvain Baize & Frédéric Jacquot & Stéphanie Reynard & Alexandra Fizet & Stephane Barron & Caroline Solas & Bruno Lacarelle & Caroline Carbonnelle & France Mentré & Hervé Raoul & Xa, 2018. "Ebola viral dynamics in nonhuman primates provides insights into virus immuno-pathogenesis and antiviral strategies," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    2. Amy Maxmen, 2018. "Experimental Ebola drugs face tough test in war zone," Nature, Nature, vol. 561(7721), pages 14-14, September.
    3. Alan S. Perelson & Avidan U. Neumann & Martin Markowitz & John M. Leonard & David D. Ho, 1996. "HIV-1 Dynamics In Vivo: Virion Clearance Rate, Infected Cell Lifespan, and Viral Generation Time," Working Papers 96-02-004, Santa Fe Institute.
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