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Link to original content: https://pubmed.ncbi.nlm.nih.gov/12368314/
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. 2002 Nov;76(21):10717-23.
doi: 10.1128/jvi.76.21.10717-10723.2002.

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

Ann H Reid  1 , Thomas G Fanning, Thomas A Janczewski, Sherman McCall, Jeffery K Taubenberger
Affiliations

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

Ann H Reid et al. J Virol. 2002 Nov.

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.

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Figures

FIG. 1.
FIG. 1.
Sequence of the 1918 matrix segment. (A) Diagram of the matrix gene segment of an influenza A virus showing the positions of the two overlapping ORFs. Nucleotides 1 to 25 and 1008 to 1027 are noncoding. The M1 and M2 ORFs share the first nine codons. (B) Sequence of the A/Brevig Mission/1/18 (H1N1) matrix gene segment coding region (GenBank accession no. AY130766). The coding sequences start at nucleotide 26; M1 and M2 share the initial nine codons. The M1 theoretical translation is shown above the line; that of M2 is shown below the line. The M2 transmembrane is boxed. The M2 ectodomain consists of the first 24 M2 protein amino acids (see also Fig. 3). The numbering of the gene segment is aligned to A/USSR/90/77 (GenBank accession no. M54941) and refers to the sequence in the sense (mRNA) orientation.
FIG. 2.
FIG. 2.
Phylogenetic trees of the Brevig18 M1 (A) and M2 (B) nucleotide sequences. Both trees are neighbor-joining trees determined by p-distance. The Brevig18 strain is indicated by an arrow. Bootstrap values are given for selected nodes, and distance bars are shown below the trees.
FIG. 3.
FIG. 3.
Alignment of M2 extracellular domain protein sequences. The first 24 residues of M2 are shown. Amino acids matching Brevig18 are shown as dots. The first 6 residues of Dk/HongKong/79 are unknown and are represented by question marks.
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