Flu Viruses Originate in Asia, Hitch Across Globe

Ker Than
for National Geographic News
April 16, 2008
The densely packed cities of East and Southeast Asia act as incubators for new strains of deadly influenza viruses that get exported around the globe, new research shows.

Two new studies show that the virus spreads in waves through cities such as Hong Kong and Bangkok before hitching rides upon human hosts to other regions.

"For over 60 years, the global migration of influenza viruses has been a mystery," said study author Colin Russell of the University of Cambridge in the United Kingdom.

Now the new findings will help scientists better predict the evolution of the most common type of influenza virus, A (H3N2), which could in turn lead to improved flu vaccines, the authors said.

(See photos of people fighting the spread of influenza.)

Evolutionary Graveyards

Russell and colleagues analyzed 13,000 samples of influenza A (H3N2) virus gathered across six continents from 2002 to 2007. Their findings appear in this week's issue of the journal Science.

The team used a new technique called antigenic cartography to make fine-grained measurements of genetic differences between strains.

They focused on the gene that encodes for hemagglutinin, a protein on the virus's protective shell that plays an important role in infection.

The team's analysis allowed them to identify different viral strains as they traveled around the world.

New strains first appeared in East and Southeast Asia and reached Europe and North America about six to nine months later.

Several months after that the viruses arrived in South America.

South America was the last to be infected because people travel less between that continent and East and Southeast Asia than they do between other parts of the world.

A key point, the authors say, is that once the strains leave their points of origin, they rarely return.

"Regions outside of East and Southeast Asia are essentially evolutionary graveyards of influenza viruses," Russell said.

The team speculates that East and Southeast Asia are good breeding grounds for the virus because of the densely packed and well-connected cities of the region.

(Related: "Killer Bird Flu Pandemic Is Preventable, Expert Says" [November 10, 2005].)

Also, unlike in North America and Europe, where flu is a seasonal occurrence that spikes in winter, influenza has a yearlong presence in the tropics.

Perfect Sense

Edward Holmes, a biologist at Pennsylvania State University, said that the team's reasoning is sound.

"To me, it makes perfect sense," Holmes said.

Holmes led a separate study, detailed in tomorrow's issue of the journal Nature, that reached similar conclusions.

Rather than comparing a single gene, Holmes' team compared the full genomic sequences of influenza viruses gathered from New York State and New Zealand.

Their results also suggested a common source of influenza viruses located somewhere in the tropics, but due to the study's limited geographic sampling, the scientists could not pinpoint it to a specific region.

The work by Holmes' team could help solve another influenza mystery, however.

For years, scientists have wondered how some influenza strains gain resistance to drugs that are not widely used, such as Tamiflu.

By sequencing the virus's full genome, the team showed that genes are linked in a complicated way.

"We show in our paper that you can't think of the evolution of [hemagglutinin] alone," Holmes said. "The whole genome evolves. It all links up."

Thus, one way influenza might be acquiring resistance to new drugs is by linking together mutations on different genes.

Kathryn Edwards is an influenza researcher at Vanderbilt University in Tennessee, who was not involved in either study.

"These are really fascinating molecular stories," Edwards said. "It's really beautiful science."

Better Forecasts

The findings could lead to improved forecasts of which strains to target when creating flu vaccines, experts say.

(Read how scientists are tracking the next killer flu.)

Currently, flu experts meet twice a year to pinpoint strains they think will pose the greatest threat the following season.

Now that scientists know the virus's Asian origins, they can better focus their energies and resources.

"There's no point in going to New York or Seattle or Buenos Aires," Holmes of Penn State said.

"The viruses are dying in those places. We need to go to the source."

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