Modeling Influenza Viral Dynamics in Tissue - Artificial Immune Systems - page 23

Modeling Influenza Viral Dynamics in Tissue

Catherine Beauchemin 1 , , Stephanie Forrest 2 , and Frederick T. Koster 3

1 Adaptive Computation Lab., University of New Mexico, Albuquerque, NM
[e-mail]
2 Dept. of Computer Science, University of New Mexico, Albuquerque, NM
3 Lovelace Respiratory Research Institute, Albuquerque, NM

Abstract. Predicting the virulence of new Influenza strains is an impor-
tant problem. The solution to this problem will likely require a combina-
tion of in vitro and in silico tools that are used iteratively. We describe
the agent-based modeling component of this program and report prelim-
inary results from both the in vitro and in silico experiments.

1 Introduction

Influenza, in humans, is caused by a virus that attacks mainly the upper respi-
ratory tract, the nose, throat and bronchi and rarely also the lungs. According
to the World Health Organization (WHO), the annual influenza epidemics affect
from 5% to 15% of the population and are thought to result in 3-5 million cases
of severe illness and 250,000 to 500,000 deaths every year around the world [1].
The rapid spread of H5N1 avian influenza among wild and domestic fowl and
isolated fatal human cases of H5N1 in Eurasia since 1997, has re-awakened inter-
est in the pathogenesis and transmission of influenza A infections [2]. The most
feared strain would mimic the 1918 strain which combined high transmissibil-
ity with high mortality [3,4]. Virulence of influenza viruses is highly variable,
defined by lethality and person-to-person transmission, but the causes of this
variability are incompletely understood. The early events of influenza replica-
tion in airway tissue, particularly the type and location of early infected cells,
likely determine the outcome of the infection. Rate of airway tissue spread is
controlled by eciency of viral entry and exit from cells, variable intracellular
interferon activation modulated by the viral NS-1 protein, and by an array of ex-
tracellular innate defenses. Although molecular biology has provided a detailed
understanding of the replication cycle in immortalized cells, influenza replica-
tion in intact tissue among phenotypically diverse epithelial cells of the human
respiratory tract remains poorly understood. We are missing a quantitative ac-
counting of kinetics in the human airway and an explanation for how one strain,
but not a closely related strain, can initiate person-to-person transmission.
Although the viral structure and composition of influenza are known, and even
some dynamical data regarding the viral and antibody titers over the course of
the infection [5,6,7], key information such as the shape and magnitude of the
viral burst, the length of the viral replication cycle (time between entry of the

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