title: The RNA polymerase PB2 subunit of influenza A/HongKong/156/1997 (H5N1) restricts the replication of reassortant ribonucleoprotein complexes [corrected].
abstract: BACKGROUND
  Genetic reassortment plays a critical role in the generation of pandemic strains of influenza virus. The influenza virus RNA polymerase, composed of PB1, PB2 and PA subunits, has been suggested to influence the efficiency of genetic reassortment. However, the role of the RNA polymerase in the genetic reassortment is not well understood.
  
  
  RESULTS
  Here, we reconstituted reassortant ribonucleoprotein (RNP) complexes, and demonstrated that the PB2 subunit of A/HongKong/156/1997 (H5N1) [HK PB2] dramatically reduced the synthesis of mRNA, cRNA and vRNA when introduced into the polymerase of other influenza strains of H1N1 or H3N2. The HK PB2 had no significant effect on the assembly of the polymerase trimeric complex, or on promoter binding activity or replication initiation activity in vitro. However, the HK PB2 was found to remarkably impair the accumulation of RNP. This impaired accumulation and activity of RNP was fully restored when four amino acids at position 108, 508, 524 and 627 of the HK PB2 were mutated.
  
  
  CONCLUSIONS
  Overall, we suggest that the PB2 subunit of influenza polymerase might play an important role for the replication of reassortant ribonucleoprotein complexes.
authors.affiliation: Division of Infectious Diseases, Department of Infectious Medicine, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakazono
authors.forename: Koyu
authors.initials: K
authors.lastname: Hara
authors.forename: Takahito
authors.initials: T
authors.lastname: Kashiwagi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
mesh_terms: D002460:Cell Line; D012321:DNA-Directed RNA Polymerases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000201:enzymology* / Q000235:genetics; D016865:Reassortant Viruses / Q000201:enzymology / Q000235:genetics; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000235:genetics / Q000502:physiology
chemical_list: D012261:Ribonucleoproteins; D014764:Viral Proteins; D012321:DNA-Directed RNA Polymerases