The role of RNA folding free energy in the evolution of the polymerase genes of the influenza A virus

Background The influenza A virus genome is composed of eight single-stranded RNA segments of negative polarity. Although the hemagglutinin and neuraminidase genes are known to play a key role in host adaptation, the polymerase genes (which encode the polymerase segments PB2, PB1, PA) and the nucleoprotein gene are also important for the efficient propagation of the virus in the host and for its adaptation to new hosts. Current efforts to understand the host-specificity of the virus have largely focused on the amino acid differences between avian and human isolates.