Characterization of the 1918 "Spanish" influenza virus matrix gene segment

Ann H Reid1, Thomas G Fanning, Thomas A Janczewski

  • 1Division of Molecular Pathology, Department of Cellular Pathology and Genetics, Armed Forces Institute of Pathology, Rockville, Maryland 20850-3125, USA. Reid@afip.osd.mil

Journal of Virology
|October 9, 2002
PubMed

Insights

The 1918 influenza A virus matrix genes (M1 and M2) were sequenced, revealing unique adaptations. Phylogenetic analysis suggests these genes were mammalian-adapted and present in human strains before 1918.

Area of Science:

  • Virology
  • Molecular Biology
  • Genetics

Background:

  • Influenza A virus RNA segment 7 encodes matrix proteins M1 and M2.
  • The 1918 pandemic virus caused significant global mortality.
  • Understanding viral evolution is crucial for pandemic preparedness.

Purpose of the Study:

  • To sequence and analyze the matrix genes (M1 and M2) of the 1918 influenza A virus.
  • To compare the 1918 matrix gene sequences with other influenza strains.
  • To infer the evolutionary origins and adaptations of the 1918 virus matrix segment.

Main Methods:

  • RNA sequencing of influenza A virus segment 7 from the 1918 pandemic strain.
  • Bioinformatic analysis of open reading frames for M1 and M2 genes.
  • Phylogenetic analysis to determine evolutionary relationships.
  • Comparison of amino acid sequences with conserved domains and known pathogenic markers.

Main Results:

  • The 1918 influenza A virus matrix segment 7 sequence is unique among previously sequenced strains.
  • Key functional domains (M1 RNA-binding, M2 transmembrane) are conserved.
  • No specific amino acid changes linked to high pathogenicity in animal models were identified in the 1918 strain.
  • Phylogenetic analyses indicate mammalian adaptation and similarity to the common ancestor of human and swine strains.
  • Four amino acids in the M2 extracellular domain match mammalian strains, suggesting pre-1918 circulation in humans.

Conclusions:

  • The matrix segment of the 1918 influenza A virus shows evidence of mammalian adaptation.
  • The sequence is closely related to the ancestor of subsequent human and swine influenza strains.
  • The findings suggest the matrix segment may have circulated in human populations for years prior to the 1918 pandemic.

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