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Published on: November 1, 2011
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
Abstract:
The coding region of influenza A virus RNA segment 7 from the 1918 pandemic virus, consisting of the open reading frames of the two matrix genes M1 and M2, has been sequenced. While this segment is highly conserved among influenza virus strains, the 1918 sequence does not match any previously sequenced influenza virus strains. The 1918 sequence matches the consensus over the M1 RNA-binding domains and nuclear localization signal and the highly conserved transmembrane domain of M2. Amino acid changes that correlate with high yield and pathogenicity in animal models were not found in the 1918 strain. Phylogenetic analyses suggest that both genes were mammalian adapted and that the 1918 sequence is very similar to the common ancestor of all subsequent human and classical swine matrix segments. The 1918 sequence matches other mammalian strains at 4 amino acids in the extracellular domain of M2 that differ consistently between avian and mammalian strains, suggesting that the matrix segment may have been circulating in human strains for at least several years before 1918.
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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