Epidemiologists have been watching H5N1 flu for years. The decimation caused by the Spanish Flu was a bit overshadowed by the press of World War I, although it killed more people than that war. It is certain that 25+ million were killed and it's estimated that unreported deaths might put that figure at 40-50 million.
We humans have no, or nearly no, immune resistance to an avian-borne influenza.
A nice pick-me-up from New Scientist:
The difference between a flu virus that kills millions, and one that kills only a few comes down to just two amino acid changes, researchers say.
The finding could allow scientists to stay one step ahead of an H5N1 flu pandemic by screening for the specific mutations that would enable it to spread.
A new study investigating the difference between the 1918 pandemic flu virus – which killed at least 50 million people – and a virus which kills but does not spread turned out to be two small mutations on the virus’s surface. Just two amino acids – the building blocks of protein – need to change on the virus’s surface in order to allow it to spread easily between people, the researchers found.
The discovery comes as H5N1 continues to kill. Indonesia this week declared a state of emergency, as it counted its 63rd death. Sub-Saharan Africa confirmed its first death, a 22 year old woman in Lagos, Nigeria.
Nose and throat
Haemagglutinin, the main surface protein on flu viruses, binds to sugars on cells in the nose and lungs; the virus then enters the cells and replicates. Bird flu prefers a sugar called 2,3-sialic acid. Flu adapted to mammals attaches better to 2,6-sialic acid. Mammals have the 2,3 sugar deep in their lungs, but 2,6 in the nose and throat.
H5N1 prefers 2,3. It had been thought that that was why it causes a devastating deep-lung infection in humans, but does not spread between people, because it does not bind and replicate in the nose.
Terrence Tumpey and colleagues at the US Centers of Disease Control in Atlanta, Georgia, US, found this was not how the 1918 virus worked. They reconstructed the virus, and changed one or two amino acids in its haemagglutinin. The combination of both of these changes transform the protein into the one found on the bird flu version of the 1918 virus.
They then gave the viruses to ferrets – animals that get flu in a way most similar to humans. The 1918 virus killed, and spread to other ferrets. One amino acid change, and it still killed, but spread poorly. Two changes, and it killed, but did not spread. Yet all the viruses replicated abundantly in the ferrets’ noses, showing that replication alone does not make a virus transmissible.
The unchanged 1918 virus binds to 2,6-sialic acid, while the ones altered by the researchers bound to 2,3. Apparently a virus that binds 2,3-sialic can nevertheless multiply in mammals’ noses after all, a finding echoed last month by scientists in Hong Kong, who found H5N1 replicates well in human nasal cells with no 2,3 sugars.
What a virus needs to spread, the CDC team concluded, is an ability to bind 2,6 sugars, whether or not it needs this to replicate. What this binding does do is not clear. One clue, they speculate, is that ferrets with non-contagious viruses – H5N1, or mutant 1918 – do not sneeze. Contagious ferrets do.
“The cells with 2,3-sialic acid receptors have been associated with the bronchial mucins,” Tumpey told New Scientist. This viscous secretion might inhibit these viruses, and prevent the irritation that causes sneezing, which “may contribute to the spread of influenza, at least in ferrets”.
But what is important is what this tells us about how the next pandemic might begin. The same mutations that made the 1918 flu contagious will not apply to H5N1, as it has a different haemagglutinin. However, the CDC results suggest finding out what mutations make H5N1 bind to 2,6-sialic, as those could make it contagious. We could then watch for those mutations to spot an emerging pandemic early.