TINY change in flu virus can switch it from merely sickening to deadly

Thursday, September 6th 2001, 12:00 am

By: News On 6

WASHINGTON (AP) _ The virus that caused the Hong Kong flu four years ago switched from a mild illness to a deadly disease when a single change occurred on one of its genes, researchers have discovered.

That tiny change allowed the flu that had been concentrated in chickens to jump to people, killing six of the 18 people infected.

``What this tells you is that the avian influenza virus can become the virus that causes the disease in humans at any moment,'' said Yoshihiro Kawaoka, one of the research team at the University of Wisconsin-Madison.

Authorities were forced to kill more than a million chickens in Hong Kong to block the spread of the newly virulent flu.

The new findings are published in Friday's issue of the journal Science.

``We have found that a limited number of very tiny genetic changes in a specific gene, one called PB2, can have a big effect on how potent the influenza virus is,'' said Kawaoka.

``Because the influenza virus constantly mutates, and because only a few changes can make a nonpathogenic virus highly pathogenic, we should assume that an outbreak of any new strain or subtype is potentially dangerous to humans,'' he said.

In a separate paper in the same journal Mark J. Gibbs and colleagues at the Australian National University in Canberra report that a new analysis of a gene from the Spanish flu that swept around the world in 1918 show that it originated from the combination of genes from pig and human flu.

The 1918 pandemic was the most severe recorded outbreak of human disease, killing over 20 million people, and the gene may hold clues to the flu's special virulence, killing an unusual number of young adults.

Robert Lamb, professor of biochemistry at Northwestern University, called Kawaota's study intriguing.

``In many ways it tells us just how complicated understanding the influenza virus is, that a point mutation in one gene can confer virulence,'' he said. ``It also tells us just how dangerous a virus influenza is.''

The disease reappeared in Hong King this summer and again more than a million chickens were slaughtered.

It has long been known that animals such as swine can harbor viruses, with major epidemics occurring when it jumps from the usual host to humans. The Hong Kong case was the first documented instance of a flu virus jumping directly from chickens to humans, according to the National Institutes of Health.

That raises particular worries because of the many live poultry markets common around the world, including parts of Florida and New York, Kawaoka said.

Viruses need to enter the cells of their hosts to reproduce. The surfaces of the virus are key to this ability, and the surface proteins of flu viruses change readily to escape detection by the human immune system. That is why new flu vaccines have to be developed each year.

Now, the Wisconsin team's report also indicates that small changes can transform a disease generally confined to the respiratory system to one that infects vital organs, including the heart and brain.

The team tested various forms of the Hong Kong virus, known as H5N1 influenza A, in mice.

They obtained samples of the viruses that had infected Hong Kong humans during the 1997 outbreak and divided them into two types, one that merely made mice sick and another that was deadly.

Then the researchers were able to study the viruses by swapping genes between them and testing how they affected mice. Through that process they discovered that the gene called PB2 from the harmful group gives the virus its potency.

Further testing allowed them to identify the changes in the gene that had the effect.

While not all the effects of the PB2 gene are known, scientists think it directs the production of an enzyme that helps force the host cell to make more viruses.

Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Disease, which supported the research, said the study ``provides insight into the emergence of virulent viruses and can help us develop better strategies for detecting future outbreaks.''