09/19/2011 06:12 EDT | Updated 11/19/2011 05:12 EST

Spanish flu virus spread in U.S. months before major outbreak, study finds

TORONTO - The virus responsible for the worst flu pandemic in known history was circulating in the United States for several months before it was recognized, new research published Monday shows.

It has been believed for years that infections in the spring of 1918 in the U.S. were a so-called "herald wave" of the Spanish flu pandemic, which eventually killed upwards of 50 million people worldwide.

But because the pandemic occurred before viruses could be isolated — before viruses were even known to exist — there hasn't been actual proof that the early cases seen in American military camps and elsewhere were caused by the same virus that wreaked such havoc on the world starting in the fall of that year.

This new study, published in the journal Proceedings of the National Academy of Sciences, provides that evidence.

Painstaking work on preserved lung tissue samples from 68 soldiers who died of influenza in 1918 reveals that the Spanish flu virus was circulating at least as early as May, said Dr. Jeffery Taubenberger, the scientist who led the work.

Nine of the deaths occurred between mid-May and early August, before the start of the major fall wave that was so deadly in North America and Europe.

Taubenberger headed the team that first found and sequenced the 1918 virus. He did that work while at the now-defunct American Forces Institute of Pathology, where the lung samples that form the basis of the new study were archived.

Taubenberger now runs a lab at the National Institutes for Allergy and Infectious Diseases in Bethesda, Md., which funded this research.

For years Taubenberger has been trying to solve the mysteries of the 1918 virus, attempting to tease out of preserved lung tissue answers to questions about the animal origins of the virus and why it was so extraordinarily lethal.

"Since the 1918 virus was this horrible, horrible, horrible virus, everyone wants to know everything about it," he said in an interview.

"Where did it come from? How did it spread? How did it start? How did it work? And yet we're dealing with something that occurred almost 100 years ago, in the pre-virology era."

An interesting feature of this work is that it showed the 1918 virus caused the same type of damage to the lungs of those who succumbed to it as did the virus behind the 2009 pandemic, which was a far more mild disease outbreak.

While that might seem counterintuitive, Taubenberger said, it probably makes sense that a fatal influenza infection would cause the same damage in the lungs, regardless of the virus responsible for it.

The work also provides some hints that the virus might have been in transition in the spring. Viruses from some of the spring cases have receptors that bind to avian cells. More of the fall cases were caused by viruses that bore receptors designed to lock onto the cells of the human respiratory tract.

Taubenberger said there isn't enough evidence to say with certainty that the spring viruses were still adapting to human hosts, but there is a suggestion that might have been the case.

Still, given the similar patterns of damage to the lungs of the fatal cases in the spring and fall, he said the findings point away from the hypothesis that the virus underwent changes in the summer of 1918 that made it more lethal.

"The answer to the mystery of why the 1918 virus killed tens of millions of people, especially young healthy adults, does not apparently live in the tissues that we look at under the microscope," he said.

However, the changing pattern of the receptors — if indeed it did occur — may have played a role in how transmissible the virus was in humans, Taubenberger said.

He insisted it's still important to figure out why the Spanish flu virus claimed so many lives.

"Because it happened once and we would certainly not want to see something like this happen again. So everything we can do to understand the past will help us prepare for the future."