Flu virus: Deadly 1918 pandemic may be the source of today’s milder seasonal flu

Viruses sequenced from century-old lung samples in German and Austrian museums have shed light on how flu can change over time

By Clare Wilson

Today’s seasonal influenza infections may be caused by direct descendants of the virus behind the 1918 flu pandemic.

That pandemic was the deadliest disease outbreak of the last century, infecting a third of the world’s population and causing up to 100 million deaths. For comparison, the current covid-19 pandemic is thought to have resulted in 15 million deaths by the end of last year.

Much about the 1918 pathogen is still mysterious: scientists only demonstrated that flu was caused by a virus in the 1930s, and few samples of the pandemic virus remain. Some of those we do have come from bodies buried in the Alaskan permafrost that remained frozen until they were dug up in the 1990s.

Now, more light has been shed by Thorsten Wolff at the Robert Koch Institute in Berlin, Germany, and his colleagues. The team genetically sequenced viruses from 13 lung samples stored in museums in Berlin and Vienna, Austria, that came from people who died from lung infections between 1901 and 1931. Three of the samples were from people who died in 1918, and two of these samples were collected before the pandemic peak in the final months of 1918.

By comparing the viruses from the 1918 samples with modern-day seasonal flu viruses, Wolff’s team found that modern viruses could have descended from the 1918 virus.

The researchers also compared the two samples of virus taken over the first few months of the 1918 pandemic with two previously sequenced pandemic viruses that had infected people later in 1918 as the pandemic peaked. They found there had been changes in a gene that encodes the nucleoprotein, a protein that surrounds the virus’s genetic material.

Previous work on cells suggests these mutations could help the virus evade human immune system defences triggered by chemicals called interferons, which target the nucleoprotein. This suggests the virus evolved to better dodge the immune system, says Wolff. “We know that this was a really virulent virus,” he says.

For the decade or so following the 1918 pandemic, deaths from flu reduced markedly, which could have been due to greater population immunity or the virus becoming less virulent, says Wolff.

Journal reference: Nature Communications, DOI: 10.1038/s41467-022-29614-9