UW researcher prepares to study new Chinese bird flu strain

Health officers examine a pigeon for H7N9
at a poultry market in Changsha, Hunan province.

The groundbreaking work of a University of Wisconsin-Madison scientist remains on hold as he awaits access to a new bird flu virus that is killing people in central-eastern China amid fears that it could leap to other countries.

"People are dying," world-renowned virologist Yoshihiro Kawaoka said in a telephone interview, explaining the urgency of research on the never-before-seen strain dubbed H7N9, which is spreading with stealth efficiency in parts of China.

Kawaoka and his team were busy unlocking the secrets of H5N1 avian influenza when their research halted more than a year ago because national health officials feared details could fall into the wrong hands and be used for bioterrorism. Others feared the dangerous virus could be accidentally released from labs in Madison and the Netherlands, where independent teams were working on similar research.

Kawaoka and other scientists warned their work was vital to preparing for the emergence of the next new avian influenza strain. And while researchers in other countries have the green light to resume research on the transmissibility of H5N1, everything funded by the U.S. National Institutes of Health remains shut down.

No human-to-human transmission of the new virus has been found in China, according to public health officials. The 28 people confirmed to have the virus - including nine who died - apparently came in close contact with infected birds, officials said.

But the new H7N9 strain is more worrisome than the H5N1 virus that Kawaoka's team has studied since 1997. Because it does not cause severe symptoms in avian species, infection with H7N9 is not as easily detected as H5N1 in domestic poultry, Kawaoka said. Many birds may carry the new strain, and humans may not realize they have it if they don't have severe symptoms, he said.

"This virus does not have features like highly pathogenic H5N1 viruses," Kawaoka said. "Unless people show severe infections, such viruses would not be looked at carefully."

Kawaoka's research was focused on identifying combinations of genetic changes that might allow a virus currently passed among animals to be spread by human-to-human contact. His team identified mutations in the H5N1 virus to make it transmissible among ferrets through coughing or sneezing.

By finding the mutations needed for the virus to jump to humans, researchers said they would be better prepared to assess the likelihood of a new virus becoming dangerous. And they would know how soon they should begin developing drugs and vaccines to stop it.

The new virus does have a specific receptor-binding mutation that Kawaoka's team and another research team in the Netherlands independently identified, which could allow the virus to bind to human cells, Kawaoka said. Avian and human viruses recognize different molecules as receptors to get into cells, he explained.

But research on the H5N1 virus in Madison and the Netherlands did identify mutations necessary for that virus to be passed among ferrets. One of those mutations has been found in the new H7N9 strain in China, Kawaoka said.

"Just having this mutation doesn't mean it could be transmissible," Kawaoka said. "For a virus to be transmitted, multiple factors are necessary."

Which factors are necessary is unknown, he said.

"That's what we wanted to research, and then we had to stop," he said.
Unprecedented step

When Kawaoka and a Dutch scientist announced in 2011 they had figured out how to make H5N1 spread among ferrets, the U.S. National Science Advisory Board for Biosecurity took the unprecedented step of seeking to censor publication of the studies.

Scientists voluntarily paused their research. Today, the transmissible H5N1 virus that Kawaoka's team identified sits in a padlocked freezer inside the UW-Madison lab waiting for a federal review panel to grant approval to resume experiments.

Kawaoka will procure the new H7N9 virus through the U.S. Centers for Disease Control and Prevention, which is working closely with Chinese and World Health Organization officials to develop a vaccine.

Some things are known about the new strain of bird flu that Kawaoka is eager to study.

Two of the eight main gene segments of the H7N9 virus seem to come from wild birds, while the other six segments come from a well-known and widely distributed poultry virus, according to scientists. But the genes have changed to acquire patterns found in human influenza viruses, causing scientists to worry whether a further evolution of the virus could increase its ability to be transmitted, the New York Times reported Monday.

Research at UW-Madison on the new virus would not involve altering its genetic makeup to study how it could become transmissible via coughing and sneezing in mammals - the process in Kawaoka's previous research that caused controversy.

Kawaoka said it's essential to characterize the properties of the H7N9 influenza virus circulating in Shanghai and three nearby provinces of central-eastern China. His team did the same thing in 2009, when it received samples of the 2009 pandemic influenza virus.

Public health officials worldwide have been closely watching the H7N9 influenza in recent weeks.

Liang Wannian, the director of the H7N9 influenza control and prevention office at China's National Health and Family Planning Commission, said at a news conference in Beijing on Monday that the government was monitoring 621 people who had been in close contact with the infected patients and had found no sign that any of them were getting sick, according to the New York Times.

All of the confirmed cases appear to be isolated, with no links between the flu strains that would suggest they were being passed from person to person, CDC director Thomas Frieden said during a teleconference.

Chinese officials are still investigating two families in which multiple cases of H7N9 are suspected, according to the World Health Organization.

One of the cases involves an 87-year-old man who died on March 4 and was later found to have had the disease. Two of his sons developed severe pneumonia about the same time, and one died on Feb. 28. While severe pneumonia is rare, H7N9 has not been confirmed in either of the sons. And even if it had, the sons, as well as their father, could have been infected through animals instead of humans.

Chinese authorities have not released details of the other family under investigation.