Just a few genetic tweaks could turn an influenza virus found in pigs into the next pandemic threat in people.
At least one virus isolated from pigs in Korea may already have potential to cause disease in people, researchers report online September 10 in the Proceedings of the National Academy of Sciences. The virus caused severe flu in ferrets, a favored proxy for humans in flu research, and grew in human lung tissue in the lab.
“That makes it a bit scary,” says study coauthor Robert Webster, a virologist at St. Jude Children’s Research Hospital in Memphis. So far, the virus has not been found in people, but “if it is in the pig, beware,” he says.
Pigs are known to be genetic mixing vessels where influenza viruses from birds, humans and pigs swap genes. The resulting viruses, called triple reassortants, are a concern because adaptations arising in pigs may help the viruses spread in humans. A triple reassortant virus that originated in pigs caused the 2009 H1N1 pandemic (SN Online: 4/27/09).
Similar triple reassortant viruses have been found among Korean pig herds, so Webster and colleagues studied several strains for their pandemic potential. Only one, known as A/Swine/Korea/1204/2009 or Sw/1204 (H1N2), made ferrets sick. That virus carries mutations in genes that help flu viruses break into and slip out of host cells. One of the mutations alters a spiky protein on the virus’s surface known as hemagglutinin. The protein helps flu viruses grab onto and invade cells in the digestive tract of birds and the respiratory system in pigs and people.
The other mutation changes a flu virus protein called neuraminidase, which slices the flu free of host cells so it can spread. Neither mutation has previously been associated with virulence, but both appear to be necessary for the virus to spread among ferrets. Flu viruses need to strike a balance between clinging tightly to host cells and cutting themselves free to infect other cells, Webster says.
Although the virus made ferrets sick in the new experiments and easily passed from ferret to ferret, there’s no guarantee the virus would behave the same way in people, says biochemist James Paulson of the Scripps Research Institute in La Jolla, Calif. Humans don’t seem to pass H1N2 flu viruses among each other, perhaps because people’s immune systems are accustomed to fighting other flu viruses that contain similar components, Paulson says.
Still, spotting these flu virus mutations in pigs may be cause for concern, says Daniel Perez, a virologist at the University of Maryland, College Park. Researchers cannot predict how a flu virus will behave just by looking at its genetic makeup, Perez says. So studies of flu virus transmission in ferrets could become early warning systems for pandemics.