The “Spanish” influenza was circulating in the population months before it peaked in the fall of 1918, according to a study published today (September 19) in the Proceedings of the National Academy of Sciences. The earlier cases could help reveal the flu’s geographic origin and how it evolved to be so infectious.

“They’ve done a really outstanding piece of work,” said Robert Webster, a virologist at St. Jude Children’s Research Hospital, who was not involved in the study. “This virus became extremely pathogenic in young men at about the time of the end of World War I,” and in order to do so it had to evolve to be more transmissible.  “This paper shows how some of the changes occurred,” he added.

The 1918 influenza, which is thought to have evolved from an avian flu, began infecting young soldiers in September of...

To find out, Taubenberger and his colleagues analyzed viral RNA from 68 autopsy samples of army recruits who had died in the months before and during the peak of the 1918 epidemic. Four of those samples came from the months of May to August, up to four months before the death toll started exploding. Consistent with later samples, early victims usually died because of pneumonia that took hold after being infected with the flu virus. The later cases didn’t seem to cause more severe disease than earlier ones.

But the researchers also found some key changes between the viruses isolated from earlier flu victims and those who died in the heat of the epidemic. Namely, in earlier cases, the hemagluttinin binding receptor, which helps the virus get a foothold in the body, was slightly more similar to that found in avian flu, while later cases showed a better fit with human hemagluttinin.  Though the newer form of the receptor didn’t seem to make the disease replicate anymore quickly, “one possibility is that the form that predominates in the later fall case might have been more transmissible,” Taubenberger said.

The findings also show that the flu was circulating earlier than previously documented. In addition, the study offers a snapshot of how the virus was evolving, and further analyses may reveal what  caused it to be so deadly.

Understanding what made this historic scourge so deadly could aid in designing treatments for modern flu, because all the flu pandemics that have occurred since are descendants of the 1918 version, Taubenberger said.

To get a more complete picture, Webster added, “it would be wonderful if they could obtain earlier clinical material for analysis to determine the precursors a little bit more about where these viruses came from.”

Z-M Sheng et al., “Autopsy series of 68 cases dying before and during the 1918 influenza pandemic peak,” Proceedings of the National Academy of Sciences, doi/10.1073/pnas.1111179108, 2011.

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