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Virus Hunters Target Swine Flu

Posted on: Tuesday, 2 June 2009, 11:40 CDT

The influenza virus is a great deceiver, changing and exchanging its coat and molecular signature between generations and among species as it eludes the body's hit men – the cells of the immune system.

In April 2009, when its toll on Mexico became public and the news was filled with blue-masked faces, Gail Demmler-Harrison, M.D., M.P.H., professor of pediatrics – infectious diseases at Baylor College of Medicine and director of the Diagnostic Virology Laboratory at Texas Children's Hospital, recognized the challenge. Faint echoes that preceded the Mexico announcement had already alerted her to the possibility that a new flu virus was circulating, long after the season had nearly died out in the United States. The new virus – finally dubbed novel H1N1 and informally known as swine flu – continues to circulate. At the end of May, the CDC reported nearly 9,000 confirmed or probable cases and 15 deaths in the United States.

Virus description

A virus-hunter already, Demmler marshaled her troops for what she knew would be a long haul – seeking to grow the virus in culture and then understand its differences and its potential for wreaking havoc. On May 22, 2009, she was part of a team led by the World Health Organization and the federal Centers for Disease Control and Prevention that published the first description of the virus and analyzed its source in an urgent report that appeared online in Sciencexpress, a companion to the journal Science.


Wendy Keitel, M.D.

That same week, Wendy Keitel, M.D., professor of molecular virology and microbiology and medicine at BCM and director of the College's federally funded Vaccine and Treatment Evaluation Unit, and colleagues began collecting samples from local swine flu patients to begin the immunological groundwork needed to develop a vaccine against the disease.

"This is all an example of incredible teamwork," said Demmler-Harrison. "It involved clinicians seeing patients and laboratories like mine in the field that were first able to grow the virus and get it to the people at the CDC quickly. It is an example of what we can do when we focus our resources."

"It was a grass roots effort, involving patients, pediatricians and experts everywhere . It's a beautiful image of what we can do together," she said.

Growing viruses

As she began to try to grow the virus, she found she had the best luck with samples from children who were in the first throes of the illness. When that became clear, physicians often hand delivered samples to her, she said.

"We were ready right then to inoculate the cell culture," she said. "There is an art to growing viruses, and my laboratory is focused on that." In an era of rapid flu tests and molecular biology – all important technologies – Demmler-Harrison and her laboratory knew that their ability to grow virus that could then be studied was priceless.

Close work with the CDC and the reference laboratory at the city of Houston Health and Human Services Department was crucial, she said.

The collaborative effort that results in that first report in Sciencexpress will prove invaluable not only in developing a vaccine against the novel H1N1 virus, but in teaching new lessons about the influenza virus itself.

"With these kinds of studies, we learn how the viruses changes and evolves as it passes from species to species. It mutates for a living," said Demmler-Harrison. "We learn how it changes within the species. This kind of basic science will help us predict how other strains might develop in the future. It is helpful to see where this virus has been, where it is now and where it might go."

Genetic sequence

At the CDC, researchers determined the genetic sequence of more than 70 samples of the virus. They determined that the virus probably came from pigs because its genetic components closely resembled those of other swine influenza viruses. The combinations of gene segments found in this virus have not been seen in previous swine influenza viruses or in those in humans.

Two genes appear similar to Eurasian swine viruses not seen outside of that geographic region previously. Six other gene segments came from a North American triple reassortment of swine viruses first detected at the end of the 1990s. They include two genes from North American avian viruses, one from human influenza H3N2 viruses and three from classic North American swine influenza viruses.

It appears to be a unique reassortment of genes that is substantially different from other known influenza viruses. It is transmissible from one human to another, but it lacks some elements that enhance such transmission or its virulence.

Seasonal vaccine provide little protection
While the proteins on its surfaces of the different virus samples were similar to each other, they were different from the seasonal form of H1N1 flu that periodically circulates among the population. This means the vaccine that protects against seasonal flu probably will provide little or no protection against this novel form.

Swine are an important reservoir of influenza virus and their influenza viruses should be monitored because they present a potential source of epidemic or even pandemic flu in the future.

Demmler-Harrison has long been on the alert against a pandemic. When she came into her laboratory on April 22, 2009, she saw an alert from California, announcing the first U.S. cases. The next day, she gave a lecture to pediatric fellows about how flu changes and the challenges it presents.

"Then it hit that weekend and for the next two to three weeks, it was exciting," she said.

"All my technicians and my laboratory manager, Jewel Greer, worked day and night," she said. "Some pulled double and triple days and even slept here. We had to mobilize quickly. It was an example of science and humanity working together. Passion sustains you through these things. My job is to hunt these viruses down and blast through them," she said.

Team work

Keitel's team worked equally as hard. While they are not making a vaccine at BCM, their efforts are aimed at finding how the body develops an immunity against the virus. That will prove crucial in vaccine trials, she said.

Keitel thinks a vaccine will be available for testing in people before the next flu season, when this novel H1N1 virus could be back, causing significant disease and even deaths – just as the seasonal flu does on a regular basis.

An estimated 36,000 people die from the flu on an annual basis, a figure that virus hunters and fighters seek to change. And they are on guard against a virulent pandemic similar to that of 1918 in which the estimated deaths worldwide were in the tens of millions.

"This is a dress rehearsal," said Demmler-Harrison. "We need to be poised to act. This is nothing compared to the drain a real pandemic would be on our resources."

She, Keitel and others at BCM will continue to hone their resources and focus their work on virus hunting and understanding influenza.

"We need to know our enemy," said Demmler-Harrison.


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