Genetic Tweak Turns Flu Virus Virulent
But discovery could lead to better vaccines
FRIDAY, Sept. 7, 2001 (HealthDayNews) -- One tiny change in a gene in the influenza virus can turn the ordinary flu into a deadly disease, new research shows.
Using a cutting-edge technology called reverse genetics, researchers at the University of Wisconsin pinpointed a minute but deadly mutation in a particularly lethal strain of influenza that showed up in Hong Kong four years ago.
The finding shows it doesn't take much to transform an ordinary virus into a killing machine, the researchers say, adding that the technology used in the discovery could lead to new and better flu vaccines. Even further down the road, they say, scientists could render flu viruses harmless so they could be used to deliver genetically engineered medicines into the human body.
"This is going to open up all kinds of opportunities to examine these viruses," says Linda Lambert, influenza program officer at the National Institute of Allergy and Infectious Diseases, which funded the research. "I think we're just beginning to see where this technology is going to take influenza."
Currently 10,000 strains of the influenza virus exist, researchers say, with wild fowl the most common carriers of the disease. Ducks, in particular, carry many strains of influenza and never get sick. But when they're mixed with chickens in live bird markets, a common cultural practice in China, the virus easily spreads to chickens and, eventually, humans.
It's this particular mutation that helps the virus thrive in a human host, the researchers say. Findings appear in today's issue of Science.
In the study, lead author Dr. Yoshihiro Kawaoka and his postdoctoral student, Masato Hatta, obtained samples of the H5N1 virus that infected 18 people and killed six during an influenza outbreak in Hong Kong in 1997.
Testing the viruses on mice, they divided the strains into two groups, one that was lethal and one that was not. Then, using the reverse genetic technology that Kawaoka streamlined in 1999, the researchers systematically swapped genes in both strains to find which gene was making the virus into a deadly killer.
They determined that the PB2 gene from the deadly strain seemed to give the virus its potency and, with more testing, discovered that a minuscule change within the gene was the key to the virulence of the virus.
Although the researchers aren't certain how the PB2 gene does its damage, they think it codes for an enzyme that helps force the host cell's molecular machinery to make more viruses.
"A small change makes a benign bug flu turn out to be a deadly one," Kawaoka says. "It happens all the time. It can happen at any moment."
And now that they've found out which mutation makes the big difference, he says, they're studying how it works and why it kicks in.
"We're in a better position to understand how influenza viruses grow in human bodies," he says. "We can develop drugs to target bad genes and proteins."
As for what can be done when influenza breaks out in the ordinary world, Kawaoka says elimination is the first line of defense. In the Hong Kong outbreak, 1 million birds were slaughtered to stop the spread of the disease.
Lambert also notes that constant surveillance can stop a deadly influenza strain before too many people are infected. In Hong Kong, they also have tried to shut down live bird markets, and most ducks are now killed before they come to market, she says.
But she says the government has given the latest information and samples of the deadly virus to a vaccine manufacturer to help the company develop stronger vaccines in the future.
What To Do
If you plan to get a flu shot this fall, and you're healthy and under 65, the federal government wants you to wait.
Hoping to avoid the havoc of last year's flu vaccine efforts, manufacturers plan to make 77 million doses, compared with the 70 million made last year. But officials say only 15 million doses are expected to be available by the end of October.
People who are not at risk can get shots in December or January and still be protected, according to the Centers for Disease Control and Prevention. So, only the elderly and those with weakened immune systems should seek shots this fall.
For more on the flu vaccine, visit the CDC online.
For everything you wanted to know about the flu, go to the National Institute of Allergy and Infectious Diseases.