Every year, Influenza virus causes major epidemics affecting between 2 to 6 million people in France. The strains responsible for these epidemics are very similar to viruses that infect other animal species, giving rise to constant fears of new emerging pandemic strains. In this context, the actual circulation of the avian Influenza virus in cattle farms in the US is being closely monitored.

The genome of Influenza A virus is made up of eight single-stranded RNA molecules of negative polarity. Each RNA segment is encapsidated by multiple copies of the viral nucleoprotein (NPs)

Extracted directly from the virus and observed by electron microscopy, RNPs appear to be intricate antiparallel double-stranded helices that are extremely flexible and highly dynamic.

In 2023, scientists from our Institut published an article to present a method to assemble nucleocapsid-like particles in vitro from recombinant NP and short RNAs. They had obtained a first parallel double-stranded helical model. This model suffered from several limitations, in particular regarding the direction of the two helical strands and the precision of the protein-RNA interactions to stabilize the integrity of the whole structure. The electron microscopy enabled the scientists to obtain a high-resolution 3D reconstruction of the parallel double-stranded helix.

The scientists now have a whole series of high-resolution 3D reconstructions to understand how NP can arrange into a helix. In particular, the antiparallel reconstruction shows how the two helices interact within this flexible architecture. The models show that while RNA is involved in structuring the helix, it can adopt different conformations.

These data also pave the way for the design of molecules that could specifically target the protein-RNA interaction of NP, to prevent its interaction with the viral RNA, thereby limiting the formation of RNPs and preventing the proliferation of Influenza virus.