Exploration and Innovation int eh Evolution of Influenza
Katia Koelle, Duke University

For many biological systems, the timescale at which ecological interactions occur is much shorter than the timescale at which evolutionary changes occur. For rapidly evolving pathogens such as influenza, however, this is not the case; influenza researchers therefore need to understand both the ecological interactions between the host and the pathogen and the virus’s evolutionary changes in order to ultimately control the disease in humans. Recently, a study looking at the evolutionary patterns of influenza showed that, while the virus’s genetic evolution occurred gradually, its antigenic evolution occurred in a punctuated manner. (Genetic evolution refers to how the virus’s nucleotides change over time; antigenic evolution refers to how the virus changes over time with respect to how our immune system recognizes it.) Previous research from our group hypothesized that these differences in evolutionary patterns could be explained by the presence of neutral networks in the virus’s genotype space: networks of sequences that differ genetically from one another but fold into the same protein conformation and thereby share antigenic properties. Here, I will present a simple epidemiological model that implicitly incorporates these neutral networks. I show that this model can reproduce (1) the seasonal and interannual outbreak patterns of influenza, (2) the quantitative patterns of influenza’s antigenic evolution, and (3) the patterns of the virus’s genetic evolution, including its characteristic phylogenetic tree. I end with how this model may be useful in understanding patterns of viral diversity in other host species (e.g., avian and swine hosts), and how this understanding could be used in the design of control strategies for pandemic influenza.

References [1-6]:

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2. Grenfell, B.T., et al., Unifying the epidemiological and evolutionary dynamics of pathogens. Science, 2004. 303: p. 327-332.

3. Koelle, K., et al., Epochal evolution shapes the phylodynamics of influenza A (H3N2) in humans. Science, 2006. 314: p. 1898-1903.

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6. Webster, R.G., et al., Evolution and ecology of Influenza A viruses Microbiological Reviews, 1992. 56(1): p. 152-179.

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