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The haemagglutinin gene, but not the neuraminidase gene, of 'Spanish flu' was a recombinant.

ABSTRACT: Published analyses of the sequences of three genes from the 1918 Spanish influenza virus have cast doubt on the theory that it came from birds immediately before the pandemic. They showed that the virus was of the H1N1 subtype lineage but more closely related to mammal-infecting strains than any known bird-infecting strain. They provided no evidence that the virus originated by gene reassortment nor that the virus was the direct ancestor of the two lineages of H1N1 viruses currently found in mammals; one that mostly infects human beings, the other pigs. The unusual virulence of the virus and why it produced a pandemic have remained unsolved. We have reanalysed the sequences of the three 1918 genes and found conflicting patterns of relatedness in all three. Various tests showed that the patterns in its haemagglutinin (HA) gene were produced by true recombination between two different parental HA H1 subtype genes, but that the conflicting patterns in its neuraminidase and non-structural-nuclear export proteins genes resulted from selection. The recombination event that produced the 1918 HA gene probably coincided with the start of the pandemic, and may have triggered it.

SUBMITTER: Gibbs MJ

PROVIDER: S-EPMC1088560 | biostudies-other | 2001 Dec

REPOSITORIES: biostudies-other

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The haemagglutinin gene, but not the neuraminidase gene, of 'Spanish flu' was a recombinant.

Gibbs M J MJ Armstrong J S JS Gibbs A J AJ

Philosophical transactions of the Royal Society of London. Series B, Biological sciences 20011201 1416

Published analyses of the sequences of three genes from the 1918 Spanish influenza virus have cast doubt on the theory that it came from birds immediately before the pandemic. They showed that the virus was of the H1N1 subtype lineage but more closely related to mammal-infecting strains than any known bird-infecting strain. They provided no evidence that the virus originated by gene reassortment nor that the virus was the direct ancestor of the two lineages of H1N1 viruses currently found in mam ...[more]

PMID: 11779383

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Project description:Which are the effects of pandemics on the returns to factors of production? Are these effects persistent over time? These questions have received renewed interest after the out-burst of deaths caused by Covid-19. The Spanish Flu is the closest pandemic to Covid-19. In this paper, we analyze the impact of the Spanish Flu on the returns to labor and capital in Spain. Spain is an ideal country to perform this exercise. First, the "excess death rate" was one of the largest in Western Europe and it varied substantially across regions. Second, Spain was transitioning towards industrialization, with regions in different stages of development. Third, Spain was developed enough to have reliable data. We identify the effect of the Spanish Flu by exploiting within-country variation in "excess death rate". Our main result is that the effect of the Spanish Flu on daily real wages was large, negative, and broadly short-lived. The effects are heterogeneous across occupations and regions. The negative effects are exacerbated in (i) occupations producing non-essential goods like shoemakers and (ii) more urbanized provinces. Quantitatively, relative to pre-1918, the decline for the average region ranges from null to around 30 percent. In addition, we fail to find significant negative effects of the flu on returns to capital. Whereas the results for dividends are imprecisely estimated (we cannot reject a null effect), the effect on real estate prices (houses and land), driven by the post-1918 recovery, is positive. Experts on inequality have argued that pandemics have equalizing effects especially in a Malthusian setting, due to real wage increases. Our findings suggest that, at least, for a developing economy like Spain in the early 20th century, this result does not apply. Indeed, we document that the flu pandemic was conducive to a (short-run) reduction in real wages. In addition, we interpret our heterogeneous results as suggestive evidence that pandemics represent a demand shock.

Project description:BackgroundCatalytic activity of influenza neuraminidase (NA) facilitates elution of progeny virions from infected cells and prevents their self-aggregation mediated by the catalytic site located in the body region. Research on the active site of the molecule has led to development of effective inhibitors like oseltamivir, zanamivir etc, but the high rate of mutation and interspecies reassortment in viral sequences and the recent reports of oseltamivir resistant strains underlines the importance of determining additional target sites for developing future antiviral compounds. In a recent computational study of 173 H5N1 NA gene sequences we had identified a 50-base highly conserved region in 3'-terminal end of the NA gene.ResultsWe extend the graphical and numerical analyses to a larger number of H5N1 NA sequences (514) and H1N1 swine flu sequences (425) accessed from GenBank. We use a 2D graphical representation model for the gene sequences and a Graphical Sliding Window Method (GSWM) for protein sequences scanning the sequences as a block of 16 amino acids at a time. Using a protein sequence descriptor defined in our model, the protein sliding scan method allowed us to compare the different strains for block level variability, which showed significant statistical correlation to average solvent accessibility of the residue blocks; single amino acid position variability results in no correlation, indicating the impact of stretch variability in chemical environment. Close to the C-terminal end the GSWM showed less descriptor-variability with increased average solvent accessibility (ASA) that is also supported by conserved predicted secondary structure of 3' terminal RNA and visual evidence from 3D crystallographic structure.ConclusionThe identified terminal segment, strongly conserved in both RNA and protein sequences, is especially significant as it is surface exposed and structural chemistry reveals the probable role of this stretch in tetrameric stabilization. It could also participate in other biological processes associated with conserved surface residues. A RNA double hairpin secondary structure found in this segment in a majority of the H5N1 strains also supports this observation. In this paper we propose this conserved region as a probable site for designing inhibitors for broad-spectrum pandemic control of flu viruses with similar NA structure.

Dataset Information

The haemagglutinin gene, but not the neuraminidase gene, of 'Spanish flu' was a recombinant.

Publications

The haemagglutinin gene, but not the neuraminidase gene, of 'Spanish flu' was a recombinant.

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