Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus

  title={Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus},
  author={Terrence M. Tumpey and Christopher F. Basler and Patricia V. Aguilar and Hui Zeng and Alicia Sol{\'o}rzano and David E. Swayne and Nancy J. Cox and Jacqueline Katz and Jeffery K. Taubenberger and Peter Palese and Adolfo Garc{\'i}a-Sastre},
  pages={77 - 80}
The pandemic influenza virus of 1918–1919 killed an estimated 20 to 50 million people worldwide. With the recent availability of the complete 1918 influenza virus coding sequence, we used reverse genetics to generate an influenza virus bearing all eight gene segments of the pandemic virus to study the properties associated with its extraordinary virulence. In stark contrast to contemporary human influenza H1N1 viruses, the 1918 pandemic virus had the ability to replicate in the absence of… 

Analysis by Single-Gene Reassortment Demonstrates that the 1918 Influenza Virus Is Functionally Compatible with a Low-Pathogenicity Avian Influenza Virus in Mice

Data suggest that the 1918 virus, whatever its origin, is very similar to avian influenza virus, and the mechanisms of influenza virus host switch, and particularly mammalian host adaptation are still only partly understood.

Reconstruction of the 1918 Influenza Virus: Unexpected Rewards from the Past

Recovery and sequence of highly degraded fragments of influenza viral RNA retained in preserved tissues from several 1918 victims eventually permitted reconstruction of the complete 1918 virus, which has yielded novel insights into influenza virus biology and pathogenesis.

Lessons learned from reconstructing the 1918 influenza pandemic.

Light is shed on what has been learned to date about the 1918 virus with regard to pathogenicity and transmissibility to supplement the understanding of the determinants of human virulence and transmission of pandemic influenza viruses.

Discovery and Characterization of the 1918 Pandemic Influenza Virus in Historical Context

The identification and sequencing of the 1918 virus, including the alleged discovery of a bacterial cause of influenza during the 1889-1893 pandemic, and subsequent breakthroughs in the 1930s that led to isolation of human and swine influenza viruses, greatly influencing the development of modern virology are placed in historical context.

Influenza pandemics: past and future

A guinea pig transmission model for influenza is developed which will help to better understand the molecular basis of virulence and the mechanisms by which pandemic influenza viruses are transmitted.

Archival influenza virus genomes from Europe reveal genomic variability during the 1918 pandemic

Comparison of genomes before and during the pandemic peak shows variation at two sites in the nucleoprotein gene associated with resistance to host antiviral response, pointing at a possible adaptation of 1918 IAV to humans.

Single gene reassortants identify a critical role for PB1, HA, and NA in the high virulence of the 1918 pandemic influenza virus

The 1918 virus virulence observed in mice correlated with the ability of 1918 recombinant viruses to replicate efficiently in human airway cells, highlighting the importance of the 1918 HA, NA, and PB1 genes for optimal virus replication and virulence of this pandemic strain.

A singular mutation in the hemagglutinin of the 1918 pandemic virus.

Emerging influenza.

  • Emmie de WitRon A M Fouchier
  • Biology
    Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology
  • 2008

Resurrected pandemic influenza viruses.

Identifying the exact genes responsible for the high virulence of the 1918 virus will be an important step toward understanding virulent influenza strains and will allow the world to better prepare for and respond to future influenza pandemics.



Initial Genetic Characterization of the 1918 “Spanish” Influenza Virus

A novel H1N1 influenza A virus that belongs to the subgroup of strains that infect humans and swine, not the avian subgroup is identified.

Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus

It is demonstrated that the HA of the 1918 virus confers enhanced pathogenicity in mice to recent human viruses that are otherwise non-pathogenic in this host.

Existing antivirals are effective against influenza viruses with genes from the 1918 pandemic virus

Recombinant viruses possessing the 1918 NA or both the 1918 HA and 1918 NA were virulent in mice, and current antiviral strategies would be effective in curbing the dangers of a re-emergent 1918 or 1918-like virus.

Pathogenicity and immunogenicity of influenza viruses with genes from the 1918 pandemic virus.

HI and virus neutralizing antibodies to 1918 recombinant and Sw/Iowa/30 viruses in human sera were present among individuals born before or shortly after the 1918 pandemic and suggest a strategy of vaccination that would be effective against a reemergent 1918 or 1918-like virus.

Sequence of the 1918 pandemic influenza virus nonstructural gene (NS) segment and characterization of recombinant viruses bearing the 1918 NS genes

The sequence of the A/Brevig Mission/1/18 (H1N1) virus nonstructural (NS) segment encoding two proteins, NS1 and nuclear export protein is reported, suggesting that interaction of the NS1 protein with host-cell factors plays a significant role in viral pathogenesis.

Origin and evolution of the 1918 "Spanish" influenza virus hemagglutinin gene.

Phylogenetic analyses suggest that the 1918 virus HA gene, although more closely related to avian strains than any other mammalian sequence, is mammalian and may have been adapting in humans before 1918.

Characterization of the 1918 "Spanish" influenza virus neuraminidase gene.

The complete coding sequence of the neuraminidase gene of the 1918 virus is determined and appears to be intermediate between mammals and birds, suggesting that it was introduced into mammals just before the 1918 pandemic.

Characterization of the 1918 “Spanish” Influenza Virus Matrix Gene Segment

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.

Novel Origin of the 1918 Pandemic Influenza Virus Nucleoprotein Gene

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.

Molecular Basis for High Virulence of Hong Kong H5N1 Influenza A Viruses

Using reverse genetics, it is shown that a mutation at position 627 in the PB2 protein influenced the outcome of infection in mice, and high cleavability of the hemagglutinin glycoprotein was an essential requirement for lethal infection.