The Dynamics of Influenza A virus Reassortment (#78)
The segmented nature of the influenza genome allows the virus to undergo reassortment (gene swapping) upon co-infection of a single cell. This process is a major contributing factor to the emergence of novel pandemic strains. In a practical context, reassortment can be utilised to produce viruses carrying the gene constellations that make them suitable for vaccine production. Despite its significance, the factors that govern gene selection during reassortment are not well understood. Using a methodology equivalent to that used for seasonal influenza vaccine seed production, we have co-infected eggs with A/Udorn/302/72 (Udorn) virus as a model seasonal strain and the egg-adapted A/Puerto Rico/8/34 (PR8) virus and tracked the genotypes throughout the reassortment process performed under the selective pressure of antibody to PR8 surface glycoproteins. In the initial stages a large variety of viruses were isolated but with subsequent rounds of growth and selection, specific gene constellations dominate. It was found that enhanced growth explained the emergence of certain gene constellations. However a few dominant viral genotypes had poor growth and we postulate that preferential packaging of gene segments drives the emergence of these viruses. Of interest, many of the final gene constellations did not maintain the three polymerase complex subunits from the same parent, despite this expectation due to their co-evolution. Overall, the PB1 and NP genes of Udorn and the PA and M genes of PR8 were found to prevail in the final viral progeny. This study of the dynamics of reassortment show it to be a largely random process initially, but selective pressures such as growth ability, gene co-selection and polymerase efficiency restrict the final viruses that dominate. Influenza virus reassortment is a complicated process and understanding the factors that govern reassortment may aid in prediction of future outbreak isolates.