Inefficient splicing of segment 7 and 8 mRNAs is an inherent property of influenza virus A/Brevig Mission/1918/1 (H1N1) that causes elevated expression of NS1 protein

Virology. 2012 Jan 5;422(1):46-58. doi: 10.1016/j.virol.2011.10.004. Epub 2011 Oct 28.

Abstract

Influenza A virus encodes two segments (7 and 8) that produce mRNAs that can be spliced. We have investigated if naturally occurring sequence polymorphisms in the influenza A virus family affects splicing of these viral mRNAs, as that could potentially alter the NS1/NS2- and/or M1/M2-protein ratios. We compared splicing efficiency of segment 7 and 8 mRNAs of A/Brevig Mission/1918/1 (H1N1) and A/Netherlands/178/95 (H3N2), as well as various H5N1 avian strains. Results revealed that both segment 7 and 8 mRNAs of A/Brevig Mission/1918/1 (H1N1) were inefficiently spliced compared to other influenza virus segment 7 and 8 mRNAs. This resulted in production of higher levels of functional NS1 protein, which could potentially contribute to the pathogenic properties of the A/Brevig Mission/1918/1 (H1N1). We also show that A/Brevig Mission/1918/1 (H1N1) segment 8 mRNAs responded differently to overexpression of SR proteins than A/Netherlands/178/95 (H3N2).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Genes, Viral
  • HEK293 Cells
  • Humans
  • Influenza A Virus, H1N1 Subtype / genetics*
  • Influenza A Virus, H1N1 Subtype / metabolism*
  • Influenza A Virus, H3N2 Subtype / genetics
  • Influenza A Virus, H3N2 Subtype / metabolism
  • Influenza A Virus, H5N1 Subtype / genetics
  • Influenza A Virus, H5N1 Subtype / metabolism
  • Plasmids
  • RNA Splicing*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Viral / genetics
  • Viral Nonstructural Proteins / biosynthesis*
  • Viral Nonstructural Proteins / genetics*
  • Viral Nonstructural Proteins / metabolism

Substances

  • INS1 protein, influenza virus
  • RNA, Messenger
  • RNA, Viral
  • Viral Nonstructural Proteins