Human importin alpha and RNA do not compete for binding to influenza A virus nucleoprotein.
Influenza virus has a segmented genome composed of eight negative stranded RNA segments. Each segment is covered with NP forming ribonucleoproteins (vRNPs) and carries a copy of the heterotrimeric polymerase complex. As a rare phenomenon among the RNA viruses, the viral replication occurs in the nucleus and therefore implies interactions between host and viral factors, such as between importin alpha and nucleoprotein. In the present study we report that through binding with the human nuclear receptor importin α5 (Impα5), the viral NP is no longer oligomeric but maintained as a monomer inside the complex. In this regard, Impα5 acts as a chaperone until NP is delivered in the nucleus for viral RNA encapsidation. Moreover, we show that the association of NP with the host transporter does not impair the binding of NP to RNA. The complex human Impα5-NP binds RNA with the same affinity as wt NP alone, whereas engineered monomeric NP through point mutations binds RNA with a strongly reduced affinity.
European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Sébastien
S
Boulo
Hatice
H
Akarsu
Vincent
V
Lotteau
Christoph W
CW
Müller
Rob W H
RW
Ruigrok
Florence
F
Baudin
D001667:Binding, Competitive; D002151:Calorimetry; D002467:Cell Nucleus / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D008958:Models, Molecular; D019590:Nucleocapsid Proteins; D017354:Point Mutation; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic; D014461:Ultracentrifugation; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D028901:alpha Karyopherins / Q000235:genetics / Q000378:metabolism*
C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D028901:alpha Karyopherins