title: The N-terminal fragment of a PB2 subunit from the influenza A virus (A/Hong Kong/156/1997 H5N1) effectively inhibits RNP activity and viral replication.
abstract: BACKGROUND
  Influenza A virus has a RNA-dependent RNA polymerase (RdRp) that is composed of three subunits (PB1, PB2 and PA subunit), which assemble with nucleoproteins (NP) and a viral RNA (vRNA) to form a RNP complex in the host nucleus. Recently, we demonstrated that the combination of influenza ribonucleoprotein (RNP) components is important for both its assembly and activity. Therefore, we questioned whether the inhibition of the RNP combination via an incompatible component in the RNP complex could become a methodology for an anti-influenza drug.
  
  
  RESULTS
  We found that a H5N1 PB2 subunit efficiently inhibits H1N1 RNP assembly and activity. Moreover, we determined the domains and important amino acids on the N-terminus of the PB2 subunit that are required for a strong inhibitory effect. The NP binding site of the PB2 subunit is important for the inhibition of RNP activity by another strain. A plaque assay also confirmed that a fragment of the PB2 subunit could inhibit viral replication.
  
  
  CONCLUSIONS
  Our results suggest that the N-terminal fragment of a PB2 subunit becomes an inhibitor that targets influenza RNP activity that is different from that targeted by current drugs such as M2 and NA inhibitors.
authors.affiliation: Department of Infection Control and Prevention, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Takahito
authors.initials: T
authors.lastname: Kashiwagi
authors.affiliation: Department of Infection Control and Prevention, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Koyu
authors.initials: K
authors.lastname: Hara
authors.affiliation: Department of Infection Control and Prevention, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakazono
authors.affiliation: Department of Infection Control and Prevention, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Uemura
authors.affiliation: Department of Infection Control and Prevention, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Imamura
authors.affiliation: Department of Infection Control and Prevention, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamada
authors.affiliation: Department of Infection Control and Prevention, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D004285:Dogs; D053124:Influenza A Virus, H5N1 Subtype / Q000737:chemistry* / Q000502:physiology; D061985:Madin Darby Canine Kidney Cells; D012261:Ribonucleoproteins / Q000037:antagonists & inhibitors*; D010948:Viral Plaque Assay; D014779:Virus Replication
chemical_list: D012261:Ribonucleoproteins