Influenza B virus has global ordered RNA structure in (+) and (−) strands but relatively less stable predicted RNA folding free energy than allowed by the encoded protein sequence

BACKGROUND: Influenza A virus contributes to seasonal epidemics and pandemics and contains Global Ordered RNA structure (GORS) in the nucleoprotein (NP), non-structural (NS), PB2, and M segments. A related virus, influenza B, is also a major annual public health threat, but unlike influenza A is very selective to human hosts. This study extends the search for GORS to influenza B. FINDINGS: A survey of all available influenza B sequences reveals GORS in the (+) and (-)RNAs of the NP, NS, PB2, and PB1 gene segments. The results are similar to influenza A, except GORS is observed for the M1 segment of influenza A but not for PB1. In general, the folding free energies of human-specific influenza B RNA segments are less stable than allowable by the encoded amino acid sequence. This is consistent with findings in influenza A, where human-specific influenza RNA folds are less stable than avian and swine strains. CONCLUSIONS: These results reveal fundamental molecular similarities and differences between Influenza A and B and suggest a rational basis for choosing segments to target with therapeutics and for viral attenuation for live vaccines by altering RNA folding stability.