The role of RNA-RNA interactions in the assembly and reassortment of influenza A viruses

Abstract

Influenza A virus has a genome consisting of 8 segments of negative sense RNA. When two influenza A virus strains infect the same cell, there is potential for the progeny to package segments from both strains. This process is termed reassortment and can lead to rapid genetic shifts that have previously generated strains of influenza responsible for pandemic events. Recent evidence suggests that assembly of the eight influenza genomic segments for packaging into a virion is mediated by RNA-RNA interactions between the segments. These interactions are likely to contribute to the varying compatibilities for reassortment observed between segments from different strains of influenza. We have captured complete RNA-RNA interaction maps for several influenza A viruses using a high-throughput sequencing approach and identify extensive, redundant, networks of RNA-RNA interactions between the genomic viral RNA segments. We extended this analysis to H1N1 and H3N2 reassortants, and found that by manipulating these interactions, we can drive preferential co-segregation of segments during reassortment. This work provides the first direct evidence that RNA-RNA interactions between the influenza virus genomic segments are a key factor in driving reassortment between viral strains.