The N-terminal region of the PA subunit of the RNA polymerase of influenza A/HongKong/156/97 (H5N1) influences promoter binding

PLoS One. 2009;4(5):e5473. doi: 10.1371/journal.pone.0005473. Epub 2009 May 7.

Abstract

Background: The RNA polymerase of influenza virus is a heterotrimeric complex of PB1, PB2 and PA subunits which cooperate in the transcription and replication of the viral genome. Previous research has shown that the N-terminal region of the PA subunit of influenza A/WSN/33 (H1N1) virus is involved in promoter binding.

Methodology/principal findings: Here we extend our studies of the influenza RNA polymerase to that of influenza strains A/HongKong/156/97 (H5N1) and A/Vietnam/1194/04 (H5N1). Both H5N1 strains, originally isolated from patients in 1997 and 2004, showed significantly higher polymerase activity compared with two classical human strains, A/WSN/33 (H1N1) and A/NT/60/68 (H3N2) in vitro. This increased polymerase activity correlated with enhanced promoter binding. The N-terminal region of the PA subunit was the major determinant of this enhanced promoter activity.

Conclusions/significance: Overall we suggest that the N-terminal region of the PA subunit of two recent H5N1 strains can influence promoter binding and we speculate this may be a factor in their virulence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chick Embryo / cytology
  • Chick Embryo / virology
  • Chickens
  • Cross-Linking Reagents
  • DNA-Directed RNA Polymerases / genetics
  • DNA-Directed RNA Polymerases / metabolism*
  • Humans
  • Influenza A Virus, H5N1 Subtype / enzymology*
  • Influenza A Virus, H5N1 Subtype / genetics
  • Kidney / cytology
  • Kidney / virology
  • Promoter Regions, Genetic / physiology*
  • RNA, Viral / metabolism*
  • RNA-Dependent RNA Polymerase / genetics
  • RNA-Dependent RNA Polymerase / metabolism*
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism
  • Transcription, Genetic
  • Ultraviolet Rays
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*
  • Virus Replication

Substances

  • Cross-Linking Reagents
  • PA protein, influenza viruses
  • RNA, Viral
  • Ribonucleoproteins
  • Viral Proteins
  • RNA-Dependent RNA Polymerase
  • DNA-Directed RNA Polymerases