Frustration and Fidelity in Influenza Genome Packaging

Abstract

Influenza genome is organized as eight distinct RNA segments, each coding for proteins essential for the virus life cycle. Post-infection, segments are replicated in the host’s nucleus and packaged into the budding progenies. Previous experimental results show that most viral progenies contain the complete genome, i.e., one copy of each of the eight segments. It is unclear how the virus efficiently assembles its genome from a pool of replicated segments. There is strong evidence suggesting that segments form specific RNA-RNA interactions and these inter-segment interactions lead to the genome assembly. However, the precise interaction network remains unresolved. Here, we investigated the nature of the interaction network by asking which network topologies would be most efficient in assembling the genome. It was shown that out of many possible network topologies, only a few of them would guarantee genome packaging. Two hypothetical models were constructed to predict the topologies that are most likely to evolve. Furthermore, the segment interaction network for Influenza virus was inferred from three published experimental datasets. This study makes testable predictions on the interactions that underlie the Influenza genome assembly, with the hope that it would provide insights into the mechanism of genome packaging and viral evolution.