Dynamics of influenza virus and human host interactions during infection and replication cycle.
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.
Department of Biology, University of Nebraska at Omaha, Omaha, NE 68182, USA.
Alex
A
Madrahimov
Tomáš
T
Helikar
Bryan
B
Kowal
Guoqing
G
Lu
Jim
J
Rogers
D003198:Computer Simulation; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity* / Q000502:physiology*; D007251:Influenza, Human / Q000188:drug therapy / Q000821:virology*; D020935:MAP Kinase Signaling System; D055641:Mathematical Concepts; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D049490:Systems Biology; D014779:Virus Replication / Q000187:drug effects
D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C