Directional Evolution of Virus Within a Host Under Immune Selection

  • Yoh Iwasa
  • Franziska Michor
  • Martin Nowak
Part of the Biological and Medical Physics, Biomedical Engineering book series (BIOMEDICAL)


Viruses, such as the human immunodeficiency virus, the hepatitis B virus, the hepatitis C virus, undergo many rounds of inaccurate reproduction within an infected host. They form a heterogeneous quasispecies and change their property following selection pressures. We analyze models for the evolutionary dynamics of viral or other infectious agents within a host, and study how the invasion of a new strain affects the composition and diversity of the viral population. We previously proved, under strain specific immunity, that (Addo et al. 2003) the equilibrium abundance of uninfected cells declines during viral evolution, and that (Bittner et al. 1997) the absolute force of infection increases during viral evolution. Here we extend the results to a wider class of models describing the interaction between the virus population and the immune system. We study virus induced impairment of the immune response and certain cross-reactive stimulation of specific immune responses. For nine different mathematical models, virus evolution reduces the equilibrium abundance of uninfected cells and increases the rate at which uninfected cells are infected. Thus, in general, virus evolution tends to increase its pathogenicity. Those trends however do not hold for general cross-reactive immune responses, which introduce frequency dependent selection among viral strains. Hence an idea for combating HIV infection is to construct a virus mutant that can outcompete the existing infection without being pathogenic itself.


Directional Evolution Successful Invasion Uninfected Cell Viral Evolution Equilibrium Number 
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© Springer-Verlag Berlin Heidelberg 2007

Authors and Affiliations

  • Yoh Iwasa
    • 1
  • Franziska Michor
    • 2
  • Martin Nowak
    • 2
  1. 1.Department of Biology, Faculty of SciencesKyushu UniversityJapan
  2. 2.Program in Evolutionary DynamicsHarvard UniversityUSA

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