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. 2004 Nov;78(22):12462-70.
doi: 10.1128/JVI.78.22.12462-12470.2004.

Novel origin of the 1918 pandemic influenza virus nucleoprotein gene

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Novel origin of the 1918 pandemic influenza virus nucleoprotein gene

Ann H Reid et al. J Virol. 2004 Nov.

Abstract

The nucleoprotein (NP) gene of the 1918 pandemic influenza A virus has been amplified and sequenced from archival material. The NP gene is known to be involved in many aspects of viral function and to interact with host proteins, thereby playing a role in host specificity. The 1918 NP amino acid sequence differs at only six amino acids from avian consensus sequences, consistent with reassortment from an avian source shortly before 1918. However, the nucleotide sequence of the 1918 NP gene has more than 170 differences from avian strain consensus sequences, suggesting substantial evolutionary distance from known avian strain sequences. Both the gene and protein sequences of the 1918 NP fall within the mammalian clade upon phylogenetic analysis. The evolutionary distance of the 1918 NP sequences from avian and mammalian strain sequences is examined, using several different parameters. The results suggest that the 1918 strain did not retain the previously circulating human NP. Nor is it likely to have obtained its NP by reassortment with an avian strain similar to those now characterized. The results are consistent with the existence of a currently unknown host for influenza, with an NP similar to current avian strain NPs at the amino acid level but with many synonymous nucleotide differences, suggesting evolutionary isolation from the currently characterized avian influenza virus gene pool.

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Figures

FIG. 1.
FIG. 1.
Sequence of the NP gene segment coding region of the 1918 strain. The coding sequence begins at nucleotide 46. The NP theoretical translation is shown above the sequence. The PIRs are boxed; within the PIRs, the PIPs are marked with asterisks. The numbering of the gene segment is aligned to that of A/WS/33 (GenBank accession number M30746).
FIG. 2.
FIG. 2.
Total nucleotide phylogenetic tree of influenza virus NP gene sequences. The tree was constructed using NJ, with the proportion of nucleotide differences as the distance measure. Bootstrap values are given for selected nodes of the tree. The position of the 1918 strain sequence is given by the arrow, and a distance bar is shown below the tree.
FIG. 3.
FIG. 3.
Changes in NP gene sequences over time. The number of nucleotide changes from a hypothetical mammalian strain ancestor were plotted versus the year of viral isolation for swine strain (closed circles) and human strain (open circles) lineages. The position of the 1918 strain sequence is shown by the arrow.

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