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Overlapping signals for translational regulation and packaging of influenza A virus segment 2

Helen M Wise1, Cyril Barbezange, Brett W Jagger

  • 1Department of Pathology, University of Cambridge, CB2 1QP, UK.

Nucleic Acids Research
|June 23, 2011
PubMed

Insights

Influenza A virus segment 2 mRNA translation is complex, involving leaky scanning and reinitiation. Short open reading frame 2 (sORF2) regulates expression of viral proteins and influences viral packaging.

Area of Science:

  • Virology
  • Molecular Biology
  • Gene Expression Regulation

Background:

  • Influenza A virus segment 2 mRNA encodes multiple proteins (PB1, PB1-F2, PB1-N40) from different start codons (AUGs).
  • Understanding the translational control mechanisms of this mRNA is crucial for comprehending viral replication and pathogenesis.

Purpose of the Study:

  • To investigate the translational regulation of Influenza A virus segment 2 mRNA.
  • To elucidate the role of short open reading frames (sORFs) and start codons in controlling the synthesis of viral proteins.

Main Methods:

  • Systematic mutation of AUG start codons (AUGs 1-4) in segment 2 mRNA.
  • Monitoring polypeptide synthesis using plasmids and recombinant influenza viruses.
  • Analysis of viral genome packaging and particle infectivity.

Main Results:

  • Short open reading frame 2 (sORF2) acts as a key regulator, differentially affecting PB1-F2 and PB1-N40 expression.
  • A model involving leaky ribosomal scanning and reinitiation explains the complex translation.
  • Mutations enhancing AUG1 initiation context in viruses led to reduced PB1 expression, poor replication, and altered virion packaging.

Conclusions:

  • Influenza A virus segment 2 mRNA translation is regulated by a combination of leaky ribosomal scanning and reinitiation mechanisms.
  • The sequences around the PB1 AUG codon contain overlapping signals for translation initiation and vRNA packaging.
  • These findings highlight multifunctional regulatory elements within viral mRNA impacting both protein synthesis and viral particle formation.

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