To most students, the flu means nothing more than a fever and several days in bed with orange juice and chicken soup. But to UW-Madison professor Yoshihiro Kawaoka, a virologist in the School of Veterinary Medicine, the flu is a part of daily life.

Kawaoka has been studying the biochemistry of influenza in poultry and mammals since the early 1980s. Most recently, he investigated the H5N1 Influenza A virus responsible for the 1997 flu outbreak in Hong Kong.

Kawaoka and post-doctoral fellow Masato Hatta have discovered the molecular basis of the virulence of the H5N1 virus that led to the 1997 outbreak. Their findings are published in the Sept. 7 edition of Science magazine.

While annual flu seasons are nothing new, the 1997 Hong Kong outbreak made international headlines because of the strain’s surprising strength. Six out of eighteen reported cases of the infection resulted in death within one month of infection.

According to Kawaoka, the influenza virus traditionally infects the respiratory system and is rarely fatal. The Hong Kong H5N1 virus, however, is particularly infectious and spreads to other organs of the body.

In mammals, the H5N1 virus has been found in the kidneys and the brain. Once these organs are affected, the body’s immune system is unable to keep up with the virus, and victims tend to die of organ failure.

The Honk Kong outbreak was unique in that it was one of the first cases in which the influenza virus had spread directly from poultry to humans. Although birds are often a source of the virus, there is usually an intermediate host the virus passes through before infecting humans.

In the case of the Hong Kong outbreak, the virus is thought to have spread directly to humans from birds?namely the chickens, ducks and quail handled in live poultry markets in Hong Kong.

Kawaoka, a native of Japan, became interested in the Hong Kong virus immediately after the 1997 outbreak. He sent a researcher to Hong Kong to collect samples from poultry markets and set out to determine why this particular influenza virus was so deadly.

From the samples, they were able to isolate two strains of virus with distinct genetic characteristics. One group of vires seemed to kill people while the other was relatively benign.

When Hatta joined Kawaoka in 1999, he used a technique known as “reverse genetics” to determine which genes were responsible for the added virulence.

“With reverse genetics we add cloned DNA from the virus to host cells, and they produce a new virus,” Hatta said.

Once these “plasmids,” as they are known, are inside the host cell, it behaves as if infected by the influenza virus, enabling researchers to monitor the outcome of the infection. By carefully controlling which plasmids are introduced to the cells, Hatta was able to pinpoint the exact gene responsible for killing the host cells.

Oddly enough, a single gene with a single mutation in its sequence is responsible for the heightened virulence of the Hong Kong strain. It appears that a change in this protein enables the virus to spread from the lungs to other vital organs, thus resulting in death.

“This mutation also allows the avian virus to grow well in humans,” Kawaoka said. “It allows for interspecies transmission.”

No more human cases of the Hong Kong virus have been reported since the 1997 outbreak, but there have been reported cases in poultry.

In May, 1.4 million chickens and ducks were slaughtered in Hong Kong and southern China due to contamination. Even after such drastic measures, the persistent virus was again detected in market poultry by mid-summer. There is fear in communities here and abroad that such an unyielding virus, which is now known to spread directly from birds, could spell trouble for human populations.

Although there have been no cases of this influenza strain reported in the United States, Kawaoka explained it is highly probable the strain will eventually emerge here.

“It is just a matter of time,” he said.

There are around 100 live poultry markets in New York and Florida, which has many researchers worried about when the virus will surface in this country.

According to Kawaoka and Hatta, at any point a relatively non-virulent virus may mutate and become highly virulent or even lethal. There is no reason to believe that such a mutation could not occur in the United States, according to Kawaoka.