Dynamics of Influenza Virus and Human Host Interactions During Infection and Replication Cycle

Alex Madrahimov, Tomáš Helikar, Bryan Kowal, Guoqing Lu, Jim Rogers

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The replication and life cycle of the influenza virus is governed by an intricate network of intracellular regulatory events during infection, including interactions with an even more complex system of biochemical interactions of the host cell. Computational modeling and systems biology have been successfully employed to further the understanding of various biological systems, however, computational studies of the complexity of intracellular interactions during influenza infection is lacking. In this work, we present the first large-scale dynamical model of the infection and replication cycle of influenza, as well as some of its interactions with the host's signaling machinery. Specifically, we focus on and visualize the dynamics of the internalization and endocytosis of the virus, replication and translation of its genomic components, as well as the assembly of progeny virions. Simulations and analyses of the models dynamics qualitatively reproduced numerous biological phenomena discovered in the laboratory. Finally, comparisons of the dynamics of existing and proposed drugs, our results suggest that a drug targeting PB1:PA would be more efficient than existing Amantadin/Rimantaine or Zanamivir/Oseltamivir.

Original languageEnglish (US)
Pages (from-to)988-1011
Number of pages24
JournalBulletin of Mathematical Biology
Volume75
Issue number6
DOIs
StatePublished - Jun 2013

Keywords

  • Computational modeling
  • Dynamical model
  • Influenza A
  • Probabilistic Boolean network
  • Systems biology

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Mathematics(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Environmental Science(all)
  • Pharmacology
  • Agricultural and Biological Sciences(all)
  • Computational Theory and Mathematics

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