Interaction network linking the human H3N2 influenza A virus genomic RNA segments.
The genome of influenza A viruses is comprised of eight negative-sense viral RNAs (vRNAs) that form viral ribonucleoproteins (vRNPs). In order to be infectious, an influenza A viral particle must encapsidate at least one copy of each of the vRNAs. Thus, even though genome segmentation is evolutionary advantageous, it undeniably complicates viral assembly, which is believed to occur through a selective mechanism that still remains to be understood. Using electron tomography 3D-reconstructions, we show that the eight vRNPs of an influenza A Moscow/10/99 (H3N2) virus are interconnected within a star-like structure as they emerge from a unique "transition zone" at the budding tip of the virions. Notably, this "transition zone" is thick enough to accommodate all described packaging signals. We also report that, in vitro, each vRNA segment is involved in a direct contact with at least one other vRNA partner, in a single network of intermolecular interactions. We show that in several cases, the regions involved in vRNA/vRNA interactions overlap with previously identified packaging signals. Our results thus provide support for the involvement of RNA/RNA interactions in the selection and specific packaging of influenza A genomic RNAs, which appear embedded into an organised supramolecular complex likely held together by direct base-pairings between packaging signals.
Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC, 15 rue René Descartes, 67084 Strasbourg, France. emifou@gmail.com
Emilie
E
Fournier
Vincent
V
Moules
Boris
B
Essere
Jean-Christophe
JC
Paillart
Jean-Daniel
JD
Sirbat
Annie
A
Cavalier
Jean-Paul
JP
Rolland
Daniel
D
Thomas
Bruno
B
Lina
Catherine
C
Isel
Roland
R
Marquet
D055032:Electron Microscope Tomography; D006801:Humans; D021621:Imaging, Three-Dimensional; D053122:Influenza A Virus, H3N2 Subtype / Q000502:physiology* / Q000648:ultrastructure; D007251:Influenza, Human / Q000821:virology; D009698:Nucleoproteins / Q000378:metabolism; D060066:Protein Interaction Maps; D012367:RNA, Viral / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*; D019065:Virus Assembly
D009698:Nucleoproteins; D012367:RNA, Viral; D014764:Viral Proteins