The 1918 “Spanish flu” was one of the most devastating pandemics in human history, killing between 50 million and 100 million people. To this day, influenza is a major health concern, with the most recent pandemic being the H1N1 flu outbreak in 2009.
“Unlike some other noteworthy diseases, like smallpox, the flu (virus) can infect many different animals, including marine life, aquatic birds and other land animals,” said Kevin Coombs, a professor of medical microbiology in the Max Rady College of Medicine at the University of Manitoba. “Therefore, there is little chance of eradicating the virus, and the virus’s genetic plasticity allows the flu to rapidly mutate to evade vaccines and antivirals.”
Many important influenza virus strains are shared between avian species, swine and humans, with pigs being a common mixing pool in which avian strains may gain the ability to infect people.
A new study, results of which were published in EBioMedicine by Coombs, Darwyn Kobasa and Charlene Ranadheera from the Public Health Agency of Canada, succeeded in measuring thousands of dysregulated cellular proteins. They noticed that many proteins not identified in earlier studies were affected by the Spanish flu.
Using state-of-the-art mass spectrometry facilities in the Manitoba Centre for Proteomics & Systems Biology at the University of Manitoba to measure upregulation and downregulation of thousands of cellular proteins after virus infection, they compared how the 1918 virus activated specific cellular pathways.
The research team, funded by the Canadian Institutes of Health Research and the Public Health Agency of Canada, found that the Spanish flu, unlike other flu viruses, induced specific and unique changes early in infection in a master cellular regulator, the Akt/mTOR pathway.
Coombs said this suggests that the Spanish flu had an unusual requirement for this cellular pathway and points the way to more focused studies to prevent future flu pandemics.
“The important differences could explain how [Spanish flu] interacts with the cells it infects. This interaction is what made the Spanish flu so deadly,” Coombs said. “Better understanding host cell responses to the flu may be the only way to stay ahead in the microbial ‘arms race’ in order to prevent re-emergence of this and of other deadly flu viruses.”