They found that slightly mutated influenza A strains in New York that circulated between 1999 and 2004 gave rise to the so-called Fujian strain that caused a troublesome outbreak in the 2003-2004 flu season.
Such events probably are what lead to the occasional pandemics of flu that can kill millions of people, David Lipman and colleagues at the National Institutes of Health found.
They hope their findings, published in the journal Public Library of Science Biology, will help scientists better predict which viral strains will attack during upcoming flu seasons and design better vaccines.
Influenza viruses are notorious for trading genes back and forth and mutating. Scientists previously believed that the gene swapping occurred gradually but the new study shows that several genes can be exchanged at once, causing sudden changes in important characteristics of the virus.
This is why a new flu epidemic sweeps the world every year, killing between 250,000 and 500,000 globally and 36,000 people in the United States alone every year.
Each year, experts must predict which strains will be most common and design a new vaccine to fight them. Some years, such as in 2003-2004, the vaccine does not include the most common strain.
Lipman and colleagues sequenced the genomes of 156 influenza A viruses, named H3N2, that were collected by New York State public health officials between 1999 and 2004.
"We found that there are co-circulating minor variants that are not infecting many people. One of these can cause the next major epidemic"
National Institutes of Health
"We found that there are co-circulating minor variants that are not infecting many people," Lipman said in a statement on Monday. "One of these can cause the next major epidemic."
They found "at least four reassortment events occurred among human viruses during the period 1999-2004" - meaning there was an exchange of genes four different times.
The newly mixed viruses, previously unnoticed because of their low virulence, suddenly became capable of infecting thousands of people.
This suggests that scientists need to study circulating flu viruses more carefully because important mutations can occur suddenly and without warning, the researchers said.
Experts say a new and deadly flu pandemic is certain to come but it is impossible to predict when. The H5N1 avian or bird flu virus, which arrived in Asia in late 2003, has so far killed more than 50 people in the region including Vietnam, Thailand and Cambodia.
Experts say the H5N1 bird flu virus
could mutate and kill millions
There is no record of it easily passing from person to person yet but health officials say it can acquire this ability at any time and if it does, it could kill millions.
A second study, published in the Proceedings of the National Academy of Sciences, found that an early wave of the 1918 "Spanish Flu" pandemic may have hit New York City several months before a big epidemic exploded globally.
The 1918-1919 pandemic was the worst in recorded history, killing as many as 40 million people.
An outbreak at the end of the previous flu season may have killed 3000 children and young adults, Donald Olson of the New York City Department of Health and colleagues found.
"The historical lesson from 20th-century influenza pandemics is that they occur in multiple waves," Olson said in a statement.