Origins of Deadly Pandemic Flu Virus of 1918 Discovered: Why it Targeted Young Adults

In 1918, a pandemic flu virus swept across the nation. This unusually severe flu resulted in the death of about 50 million people. Now, researchers have found the origin of this flu virus and the reason behind its unusual severity, revealing new clues about the flu viruses of today.

"Ever since the great flu pandemic of 1918, it has been a mystery where that virus came from and why it was so severe, and in particular, why it killed young adults in the prime of life," said Michael Worobey, one of the researchers, in a news release. "It has been a huge question what the ingredients for that calamity were, and whether we should expect the same thing to happen tomorrow, or whether there was something special about that situation."

In order to answer these questions, the scientists developed an accurate molecular clock approach. Using this technique, they reconstructed the origins of the 1918 H1N1 influenza A virus (IAV), the classical swine H1N1 influenza virus and the post-pandemic seasonal H1N1 lineage that circulated from 1918 until 1957.

So what did they find? It turns out that they found no hard evidence of two prevailing theories of the 1918 virus-that it jumped directly from birds or that it involved the swapping of genes between existing human and swine influenza strains. Instead, they found that the virus arose shortly before 1918 upon the acquisition of genetic material from a bird flu virus by an already circulating human H1 virus, one that had likely entered the human population a decade beforehand.

The researchers found that if individuals had already been exposed to an H1 virus, they could have experienced much lower death rates than those who died in the greatest numbers-a cohort that centered around those who were 29 years of age. It's possible that this was the case since many young adults were exposed during childhood to a putative H3N8 virus circulating in the population. This virus featured surface proteins distinct to both the major antigenic proteins of the H1N1 virus. In other words, they were uniquely susceptible to severe disease. The elderly, in contrast, might have been exposed in youth to an H1N1-like virus, making them more immune.

"What seems to be the decisive factor is prior immunity," said Worobey in a news release. "Our study takes a variety of observations that have been difficult to explain and reconciles and places them into a logical chain able to explain many patterns of influenza mortality over the last 200 years."

The findings are published in the journal Proceedings of the National Academy of Sciences.